Search Results (166)

(1) Background: Monomorphic intestinal epitheliotropic T-cell lymphoma (MEITL) is a very rare subtype of lymphoma, being involved in less than 5% of lymphomas of the digestive tract. Accurate diagnosis is extremely challenging due to the lack of specific clinical symptoms and the low specificity of the diagnostic approaches. (2) Methods: We present the case of a patient admitted to the Neurology Clinic of the Emergency Clinical Hospital of Galati, Romania, with progressive cranial nerve impairment. (3) Results: Analyzing clinical and paraclinical data and corroborating the previous known diagnosis of MEITL, the positive diagnosis was that of meningitis with atypical lymphocytes with MEITL as starting point. The cytology of CSF was the basis for the diagnostic confirmation. (4) Conclusions: The present case is a rare situation of secondary dissemination of MEITL. We were not able to identify a similar report in the available literature that associated urothelial carcinoma with leptomeningeal MEITL-sourced neoplastic lesions. Full article

Central nervous system metastases involving the brain parenchyma and leptomeninges are common in non-small cell lung cancer, especially cases with EGFR mutations. Here, we examine treatment options for EGFR-mutated non-small cell lung cancer patients with central nervous system metastases, highlighting the efficacy of third-generation EGFR-targeted tyrosine kinase inhibitors. Furthermore, we examine the interplay of this modality with chemotherapy or radiation in resistant cases. Full article

Introduction: Acute Myeloid Leukemia (AML) is a hematologic malignancy characterized by the clonal expansion of myeloid progenitors. While it primarily affects the bone marrow, extramedullary relapse occurs in 3–5% of cases, and it is linked to poor prognosis. Central nervous system (CNS) involvement presents diagnostic challenges due to nonspecific symptoms. CNS manifestations include leptomeningeal dissemination, nerve infiltration, parenchymal lesions, and myeloid sarcoma, occurring at any disease stage and frequently asymptomatic. Methods: A 62-year-old man with a recent history of AML in remission presented with diplopia and aching paresthesias in the left periorbital region spreading to the left frontal area. The diagnostic workup included neurological and hematological evaluation, lumbar puncture, brain CT, brain magnetic resonance imaging (MRI) with contrast, and dermatological evaluation with skin biopsy due to the appearance of nodular skin lesions on the abdomen and thorax. Results: Neurological evaluation showed hypoesthesia in the left mandibular region, consistent with left trigeminal nerve involvement, extending to the periorbital and frontal areas, and impaired adduction of the left eye with divergent strabismus in the primary position due to left oculomotor nerve palsy. Brain MRI showed an equivocal thickening of the left oculomotor nerve without enhancement. Cerebrospinal fluid (CSF) analysis initially showed elevated protein (47 mg/dL) with negative cytology; a repeat lumbar puncture one week later detected leukemic cells. Skin biopsy revealed cutaneous AML localization. A diagnosis of AML relapse with CNS and cutaneous localization was made. Salvage therapy with FLAG-IDA-VEN (fludarabine, cytarabine, idarubicin, venetoclax) and intrathecal methotrexate, cytarabine, and dexamethasone was started. Subsequent lumbar punctures were negative for leukemic cells. Due to high-risk status and extramedullary disease, the patient underwent allogeneic hematopoietic stem cell transplantation. Post-transplant aplasia was complicated by septic shock; the patient succumbed to an invasive fungal infection. Conclusions: This case illustrates the diagnostic complexity and poor prognosis of extramedullary AML relapse involving the CNS. Early recognition of neurological signs, including cranial nerve dysfunction, is crucial for timely diagnosis and management. Although initial investigations were negative, further analyses—including repeated CSF examinations and skin biopsy—led to the identification of leukemic involvement. Although neuroleukemiosis cannot be confirmed without nerve biopsy, the combination of clinical presentation, neuroimaging, and CSF data strongly supports the diagnosis of extramedullary relapse of AML. Multidisciplinary evaluation remains essential for detecting extramedullary relapse. Despite treatment achieving CSF clearance, the prognosis remains unfavorable, underscoring the need for vigilant clinical suspicion in hematologic patients presenting with neurological symptoms. Full article

Background and Clinical Significance: Non-small-cell lung cancer (NSCLC) with EGFR mutations, particularly de novo compound mutations such as exon 19 deletions (Ex19del) with T790M substitutions, present a significant clinical challenge due to resistance to many treatments. While treating these patients, the administration of osimertinib, a third-generation EGFR inhibitor, after immunotherapy can lead to unique immune-related adverse events (irAEs), such as pneumonitis and, rarely, hepatitis. Case Presentation: A 36-year-old Filipino woman presented with metastatic NSCLC harboring de novo Ex19del and T790M mutations. Despite initial therapy with carboplatin and paclitaxel, followed by chemoimmunotherapy, the patient’s disease progressed. She subsequently developed severe hepatitis from osimertinib after her prior immunotherapy with pembrolizumab. After the hepatitis resolved with high-dose steroids, osimertinib was switched to afatinib, but her disease rapidly progressed with new metastases. A second attempt at osimertinib rechallenge, with concomitant prednisone, resulted in substantial disease control, including improved leptomeningeal disease (LMD) and no recurrence of hepatitis. Conclusions: This case underscores the feasibility of rechallenging with osimertinib in patients who experience adverse events such as hepatotoxicity, provided that appropriate management strategies, such as steroid therapy, are employed. The successful rechallenge in this case highlights the potential of osimertinib as a viable option in advanced EGFR-mutant NSCLC, even after prior treatment-related complications. Full article

Background and Clinical Significance: The mesenchymal–epithelial transition (MET) exon 14 skipping mutation (METex14) is a rare genetic alteration occurring in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) are the approved treatment for first-line therapy in a metastatic setting. However, the unusual presentation of gastrointestinal metastasis and leptomeningeal carcinomatosis (LMD) poses significant treatment challenges. Case Presentation: Here we report a case of a 72-year-old male with metastatic METex14-positive NSCLC, presenting with brain and duodenal metastases. Conclusions: The patient responded exceptionally well to first-line chemoimmunotherapy, achieving clinically complete remission for 2 years. He subsequently developed cerebellar metastasis and leptomeningeal disease (LMD) but demonstrated a remarkable response to tepotinib and continued to enjoy radiographic complete remission over 2.5 years at the time of this report. Full article

Background: Cerebral amyloid angiopathy (CAA) represents a progressive cerebrovascular disorder, characterized by aberrant accumulation of beta-amyloid isoforms in cortical and leptomeningeal vessel walls of cerebrum and cerebellum. Methods: We sought to investigate the clinical manifestations, current different diagnostic tools, various therapeutic strategies and most uncommon subtypes of the disease. Results: The vast majority of CAA remains sporadic, with increasing prevalence with age and very frequent coexistence with Alzheimer’s disease. Clinically, CAA can present with spontaneous lobar intracerebral hemorrhage, transient focal neurologic episodes attributed to convexity subarachnoid hemorrhage or cortical superficial siderosis, and progressive cognitive decline leading to dementia. Inflammatory CAA subtype should be recognized early and treated promptly so that better functional outcomes may be achieved. Moreover, genetic and iatrogenic CAA forms are rare, yet increasingly recognized during the last years. Therapeutic management remains challenging for clinicians, especially when markers indicative of higher bleeding risk are present. A targeted therapy does not currently exist. However, various clinical trials are in progress, focusing on offering new promising insights into the disease treatment. Conclusions: This review aims to deepen our understanding of CAA diagnosis and therapeutic approach but also summarizes current evidence on the most uncommon subtypes of this cerebral small-vessel disease. Full article

To evaluate the factors influencing the outcomes of patients who underwent surgical resection of brain metastasis followed by either surveillance or post-operative stereotactic radiosurgery/fractionated radiotherapy (SRS/SFRT), a retrospective multi-center chart review was performed on all patients who underwent brain metastases resection in British Columbia between 2018 and 2020. Patients with prior whole-brain radiotherapy were excluded from the study. The primary study endpoints included local recurrence, distant intracranial control, radionecrosis (RN), leptomeningeal disease (LMD), and overall survival (OS). The Kaplan–Meier method was used to analyze survival. The Cox proportional hazards model was used to perform univariable (UVA) and multivariable (MVA) analyses to identify predictors of local control. A total of 113 patients met the inclusion criteria. A total of 31 patients received adjuvant SRS/SFRT to the surgical cavity, while 82 went on observation. The 12-month local control was 69% (50–88%) for the SRS/SFRT cohort and 31% (18–45%) for the observation cohort (p < 0.001). The 12-month distant intracranial control was 44% (26–63%) for the SRS/SFRT cohort and 46% (30–62%) for the observation cohort (p = 0.9). Sensitivity analysis did not show a difference in overall survival (p = 0.6). En bloc resection (p < 0.05), resection without residual disease (p < 0.05), and SRS/SFRT (p < 0.001) were predictive of local control on MVA. Three SRS/SFRT patients (10%) and two observation patients (2%) developed LMD. Four SRS/SFRT patients experienced RN (13%), with no grade 3 or higher toxicities observed. Post-operative SRT outcomes based on real-world population data are consistent with the data from clinical trials and support the established guidelines. For patients requiring surgical resection of brain metastasis, en bloc gross total resection should be encouraged when feasible to reduce local recurrence. Full article

Background: Hyperintense vessels (HVs) visualized on FLAIR MRI are believed to reflect sluggish antegrade or retrograde flow in leptomeningeal collaterals that develop in response to major intracranial artery stenosis or occlusion. HV is frequently observed in conditions such as Moyamoya disease and symptomatic ICA/MCA steno-occlusion. However, the relationship between HV and cerebral hemodynamics—and the effect of STA-MCA bypass on HV—remains inadequately characterized. This study aimed to investigate the relationship between HV on FLAIR and cerebral vascular hemodynamic status, as measured by SPECT, in patients with Moyamoya disease and symptomatic ICA/MCA occlusion. The secondary goal was to assess the impact of recanalization through STA-MCA bypass surgery on the presence of HV. Methods: We retrospectively analyzed 49 patients with symptomatic ICA or MCA steno-occlusion who underwent STA-MCA bypass between 2015 and 2020. Pre- and postoperative FLAIR MRIs were evaluated, and HV presence was graded as negative (0), minimal (1), or positive (2). SPECT was utilized to assess cerebrovascular reserve (CVR) in regions exhibiting various HV intensities. Follow-up FLAIR imaging was performed 3–14 months postoperatively to correlate HV changes with hemodynamic improvements observed via SPECT. Result: HV was present in 74% (36/49) of affected hemispheres. Regions exhibiting minimal or positive HV demonstrated a significantly lower CVR compared to HV-negative areas, indicating compromised perfusion. Following bypass surgery, HV was reduced or resolved in 65% (32/49) of patients, and this regression corresponded with improved CVR as confirmed by both SPECT and perfusion MRI. Conclusions: HV presence on FLAIR imaging is associated with impaired cerebrovascular hemodynamics in patients with Moyamoya disease or symptomatic large-vessel steno-occlusion. HV-positive territories exhibit reduced CVR, while surgical revascularization via STA-MCA bypass leads to hemodynamic improvement and concurrent HV reduction. These findings support HV as a potential surrogate marker for treatment response. Full article

Background/Objectives: Neurosurgical resection is the standard treatment for large brain metastases (BMs). Postoperative stereotactic radiotherapy (SRT) is used to reduce local recurrence (LR) but does not always prevent leptomeningeal disease (LMD). This study aims to analyze patterns of tumor recurrence and to identify opportunities for the further improvement of treatment efficacy. Methods: We included 147 patients who underwent resection and SRT for BMs. The distance between the resection cavity target volume and the new tumor growth was calculated. Cox regression analyses were used to assess associations of LMD with various patient characteristics. Results: Median survival after postoperative SRT was 14 months (IQR 6–30) with a 3-year actuarial survival rate of 21%. LR occurred in 20/147 patients (14%). After total resection, LR occurred in 21% of patients after 3 years of follow-up compared to 36% after subtotal resection. Marginal LR occurred in 5/147 patients (3%). LMD was found in 21/147 patients (14%; 3-year actuarial rate, 26%), and it was found more commonly in patients with resected cerebellar metastases (23%; 3-year actuarial rate, 46%) compared to those with cerebral metastases (11%; 3-year actuarial rate 17%) (HR 2.54, 95% CI 1.07–6.04, p = 0.034). Conclusions: This study examined patterns of recurrence after postoperative radiotherapy and its implications for radiation dose, radiation field size, and treatment sequence. Local control was high after total resection. Radiation field size appeared adequate given the low incidence of marginal recurrences. Patients with cerebellar metastases showed an increased risk of LMD, underscoring the need for preventive measures, particularly preoperative SRT. Full article

Background. Sturge–Weber syndrome (SWS) is a rare non-hereditary neurovascular disorder characterized by capillary–venous malformations on the face, ocular vascular anomalies, and leptomeningeal capillary–venous malformations. Patients with SWS often experience cerebral perfusion impairment, increasing their risk for stroke-like episodes, seizures, and motor and cognitive impairments. Methods. We report the case of a 2-year-old boy diagnosed with SWS who developed a stroke-like episode following dye laser therapy under deep sedation. Results. Despite initial diagnostic challenges and persistent seizures, appropriate management led to full neurological recovery. Conclusions. This case highlights the importance of considering stroke-like episodes in children with SWS after stressful events such as medical procedures. Full article

Background: In metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, osimertinib is the cornerstone treatment able to prolong overall survival (OS). Evidence around osimertinib being effective in leptomeningeal metastasis (LM) is scarce. Methods: We conducted a retrospective cohort study of patients with metastatic NSCLC-EGFR mutation treated with osimertinib at Sunnybrook Hospital. Results: We identified a total of 56 patients. Of these, 45 (79.4%) were never smokers, 53 (94.6%) had adenocarcinoma histology, and 26 (46.42%) had either the EGFR exon 21-L858R mutation or exon 19 deletion. The estimated median OS was 51 months (43.5–58.5). All eight patients with LM died during the study period. From the time of NSCLC diagnosis, the OS of patients without LM was 53 months (95% CI 47.2–58.7), and with LM was 21 months (95% CI 3.0–39), p = 0.001. However, the median OS from LM diagnosis was 2 months (95% CI, 1.0–26). Conclusions: In our population of patients with metastatic NSCLC-EGFR mutation who received osimertinib, there was a significant reduction in life expectancy in the group with LM. Patients who had advanced stage at diagnosis and were more likely to develop LM exhibited poorer survival compared to those who had early-stage cancer at diagnosis and developed metastases later on. Full article

Good leptomeningeal collaterals (LMCs) after large vessel occlusion (LVO) extend the time window for endovascular therapy. The mechanisms regulating LMC activation are not fully understood. The aim of this study was to investigate the potential role of two vasoactive molecules endothelin-1 (ET-1)—a vasoconstrictor agent—and nitric oxide (NO)—a vasodilator agent—in the regulation of post-stroke LMCs. Ischemic stroke patients within 6 h of LVO were included. Collateral status was assessed using the Menon scoring system based on computed tomography angiography scans. Patients were accordingly divided into three groups: poor, intermediate, and good LMCs. Recanalization was evaluated using the modified thrombolysis in cerebral infarction (mTICI) score. Serum levels of ET-1 and NO were measured at three time points: T0 (<6 h), T1 (24 h), and T2 (48 h). A total of 105 patients were enrolled (mean age 76 ± 12.8 years): 44 with good (46.2%), 36 with intermediate (37.8%), and 22 with poor LMCs (23.1%). NO values decreased, whereas ET-1 values increased from T0 to T1 in all groups of patients. No significant association was found between serum ET-1 levels and collateral status. Higher ET-1 levels at T1 correlated with poor outcome regardless of the LMC status or the degree of recanalization (p = 0.030). A significant linear positive correlation was revealed at T0 between high levels of ET-1 and the neutrophil count (Spearman’s rho = 0.236, p = 0.035). Subgroup analysis showed a significant inverse correlation at T1 between NO and the collateral score (Spearman’s rho = −0.251, p = 0.021). Although we observed no significant association between LMC score and serum ET-1 concentrations, at 24 h higher ET-1 serum levels were predictive of poor outcome and higher NO levels were correlated with poor collateral status. These findings may indicate an inadequate microvascular reperfusion, possibly due to ET-1-mediated vasoconstriction, neutrophil activation, and NO-mediated oxidative stress, suggesting their potential role in the no-reflow phenomenon. Full article

Sturge–Weber Syndrome (SWS) is a rare neurocutaneous disorder caused by a somatic nonsynonymous mosaic mutation most commonly in the GNAQ gene (G protein guanine Nucleotide-binding protein Alpha subunit q). SWS is characterized by capillary-venous malformations in the brain and eyes and a characteristic facial port wine (PW) birthmark (previously called port wine stain/PWS) in the head/neck region. Clinical manifestations vary and include epilepsy, stroke-like episodes, migraine headaches, cognitive delays, glaucoma, ocular vascular anomalies, heterochromia of the iris, visual field defects, and endocrine disorders like growth hormone deficiency or central hypothyroidism. The pathognomonic findings seen in neuroimaging with magnetic resonance imaging (MRI) include the presence of unilateral intracranial leptomeningeal angiomatosis, typically ipsilateral to the facial birthmark. SWS does not currently have a definitive cure, and management strategies focus on symptomatic management such as anti-seizure medications, limited surgical resection of the epileptogenic tissue or hemispherectomy for cases of drug-resistant epilepsy (DRE), selective photo-thermolysis of the PWS using a pulsed dye laser, and the medical and/or surgical management of glaucoma. In addition to these symptomatic treatments, the use of preventive, modifying, or stabilizing treatments like low-dose aspirin in reducing the frequency and severity of seizures and stroke-like events and the use of newer therapies like cannabidiols and mTOR inhibitors are being reviewed and have shown promising early results. This comprehensive narrative review summarizes the current literature on clinical management strategies, ongoing research studies, and future directions in the diagnosis and management of SWS. Full article

Cerebral amyloid angiopathy (CAA) is one of the most prevalent small vessel diseases (SVDs). Its neuroradiological hallmarks are both hemorrhagic and non-hemorrhagic ones. Among the clinical manifestations, transient focal neurological episodes (TFNEs) are associated with an increased risk of bleeding in a short time period and with convexal subarachnoid hemorrhage (SAH). The natural history of CAA is incompletely characterized in the literature, because the focus has been mostly on hemorrhagic events, while both clinical and non-hemorrhagic presentations are possible and sometimes underestimated. Furthermore, new diagnostic criteria have incorporated non-hemorrhagic Magnetic Resonance Imaging (MRI) markers and non-hemorrhagic clinical presentations. Disease trajectories are often individual and help provide food for thought and discussion on some issues, thus allowing for a greater and deeper evaluation. We, therefore, present a case that exemplifies how the natural history of CAA can be atypical compared to its expected course, which is long and not only hemorrhagic. Several episodes of CAA-related inflammation, with prevalent, but not exclusive, leptomeningeal involvement, were evaluated and treated in the presented case, in which the intraparenchymal cerebral hemorrhagic manifestation was the last in the patient’s history. CAA may have a very long natural history. During the disease’s course, inflammatory features might be prominent in neuroimaging but not strongly symptomatic, and intraparenchymal cerebral hemorrhage (ICH) may be a late event. The awareness of this subtype of the disease allows us to better explore the pathophysiology of CAA and to increase the level of clinical suspicion for the diagnosis. Furthermore, the distinction between different disease phenotypes can provide useful information for patient management in clinical practice. Full article