A new perspective on the role of the frontoparietal regions in Stroop-like conflicts.

Humans are goal-directed; however, goal-unrelated information still affects us, but how? The Stroop task is often used to answer this question, relying on conflict (incongruency) between attributes, one targeted by the task and another irrelevant to the task. The frontal regions of the brain are known to play a crucial role in processing such conflict, as they show increased activity when we encounter incongruent stimuli. Notably, the Stroop stimuli also consist of conceptual dimensions, such as semantic or emotional content, that are independent of the attributes that define the conflict. Since the non-targeted attribute usually refers to the same conceptual dimension as the targeted-attribute, it is relevant to the task at hand. For example, when naming the emotion of an emotional face superimposed by an emotional word, both the targeted-attribute and the non-targeted attribute refer to the conceptual dimension "emotion". We designed an fMRI paradigm to investigate how conflicts between different conceptual dimensions impact us. Even though the conflict was task-irrelevant, incongruent stimuli resulted in longer reaction times, indicating a behavioral congruency effect. When examining the neural mechanisms that underlie this effect, we found that the frontal regions exhibited repetition suppression, while the bilateral intraparietal sulcus (IPS) showed a congruency effect linked to the behavioral effect. Taken together, these findings suggest that individuals are unable to completely ignore task-irrelevant information, and that the IPS plays a crucial role in processing such information.

Aberrant paramagnetic signals outside the tumor volume on routine surveillance MRI of brain tumor patients.

Late complications of cerebral radiation therapy (RT) involve vascular injury with acquired cavernous malformation, telangiectasias and damage to vascular walls which are well recognized in children. Its incidence in adults is unknown. Blood products and iron deposition that accompany vascular injury create paramagnetic effects on MRI. This study retrospectively investigated the frequency of paramagnetic lesions on routine surveillance MRI of adult brain tumor patients. MRI studies of 115 brain tumor patients were reviewed. Only studies containing sequences of either susceptibility weighted images or gradient echo or blood oxygenation level dependent imaging were included. Lesions inside the tumor volume were not considered. 68 studies fulfilled the above criteria and included 48 patients with previous RT (35 followed for >2 years and 13 for 1 year) and 20 patients who were not treated with RT. The median age at time of irradiation was 47 years. Aberrant paramagnetic lesions were found in 23/35 (65%) patients followed for >2 years after RT and in only 1/13 (8%) patients followed for 1-year after radiation (p = 0.03). The 1-year follow-up group did not differ from the control group [2/20 (9%)]. Most lesions were within the radiation field and none of the patients had related symptomatology. The number and incidence of these lesions increased with time and amounted to 75% over 3 years post RT. MRI paramagnetic signal aberrations are common findings in adult brain tumor patients that evolve over time after RT. The clinical significance of these lesions needs further investigation.

Clinicoradiologic Criteria for the Diagnosis of Stroke-like Episodes in MELAS.

Background and Objectives: Stroke-like episodes (SLEs) in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome are often misdiagnosed as acute ischemic stroke (AIS). We aimed to determine unique clinical and neuroimaging features for SLEs and formulate diagnostic criteria. Methods: We retrospectively identified patients with MELAS admitted for SLEs between January 2012 and December 2021. Clinical features and imaging findings were compared with a cohort of patients who presented with AIS and similar lesion topography. A set of criteria was formulated and then tested by a blinded rater to evaluate diagnostic performance. Results: Eleven MELAS patients with 17 SLE and 21 AISs were included. Patients with SLEs were younger (median 45 [37-60] vs 77 [68-82] years, p < 0.01) and had a lower body mass index (18 ± 2.6 vs 29 ± 4, p < 0.01), more commonly reported hearing loss (91% vs 5%, p < 0.01), and more commonly presented with headache and/or seizures (41% vs 0%, p < 0.01). The earliest neuroimaging test performed at presentation was uniformly a noncontrast CT. Two main patterns of lesion topography with a stereotypical spatiotemporal evolution were identified-an anterior pattern (7/21, 41%) starting at the temporal operculum and spreading to the peripheral frontal cortex and a posterior pattern (10/21, 59%) starting at the cuneus/precuneus and spreading to the lateral occipital and parietal cortex. Other distinguishing features for SLEs vs AIS were cerebellar atrophy (91% vs 19%, p < 0.01), previous cortical lesions with typical SLE distribution (46% vs 9%, p = 0.03), acute lesion tissue hyperemia and venous engorgement on CT angiography (CTA) (45% vs 0%, p < 0.01), and no large vessel occlusion on CTA (0% vs 100%, p < 0.01). Based on these clinicoradiologic features, a set of diagnostic criteria were constructed for possible SLE (sensitivity 100%, specificity 81%, AUC 0.905) and probable SLE (sensitivity 88%, specificity 95%, AUC 0.917). Discussion: Clinicoradiologic criteria based on simple anamnesis and a CT scan at presentation can accurately diagnose SLE and lead to early administration of appropriate therapy. Classification of Evidence: This study provides Class III evidence that an algorithm using clinical and imaging features can differentiate stroke-like episodes due to MELAS from acute ischemic strokes.

Assessment of response of brain metastases to radiotherapy by PET imaging of apoptosis with ¹8F-ML-10.

PURPOSE: Early assessment of tumor response to therapy is vital for treatment optimization for the individual cancer patient. Induction of apoptosis is an early and nearly universal effect of anticancer therapies. The purpose of this study was to assess the performance of (18)F-ML-10, a novel PET radiotracer for apoptosis, as a tool for the early detection of response of brain metastases to whole-brain radiation therapy (WBRT). MATERIALS AND METHODS: Ten patients with brain metastases treated with WBRT at 30 Gy in ten daily fractions were enrolled in this trial. Each patient underwent two (18)F-ML-10 PET scans, one prior to the radiation therapy (baseline scan), and the second after nine or ten fractions of radiotherapy (follow-up scan). MRI was performed at 6-8 weeks following completion of the radiation therapy. Early treatment-induced changes in tumor (18)F-ML-10 uptake on the PET scan were measured by voxel-based analysis, and were then evaluated by correlation analysis as predictors of the extent of later changes in tumor anatomical dimensions as seen on MRI scans 6-8 weeks after completion of therapy. RESULTS: In all ten patients, all brain lesions were detected by both MRI and the (18)F-ML-10 PET scan. A highly significant correlation was found between early changes on the (18)F-ML-10 scan and later changes in tumor anatomical dimensions (r = 0.9). CONCLUSION: These results support the potential of (18)F-ML-10 PET as a novel tool for the early detection of response of brain metastases to WBRT.

Pituitary-directed medical therapy with pasireotide for a corticotroph macroadenoma: pituitary volume reduction and literature review.

Hypercortisolism due to an ACTH-secreting pituitary adenoma (Cushing's disease) is a chronic condition associated with high morbidity and mortality if inadequately managed. Pasireotide is a multireceptor-targeted somatostatin analogue and is the only approved medical therapy for Cushing's disease that treats the underlying cause of the disorder. This paper reviews the available literature for medical-therapy-induced adenoma volume reduction in patients with Cushing's disease and reports the experience of a 53-year-old surgically, radiologically and medically naïve (de novo) female with a pituitary macroadenoma who declined surgery. This patient was treated with pasireotide as first-line therapy as part of the largest randomized Phase III study evaluating a medical therapy in patients with Cushing's disease (SOM230B2305 trial). Subcutaneous pasireotide significantly decreased tumor volume, suppressed cortisol secretion, and improved clinical signs and symptoms of Cushing's disease in this patient. Based on this experience, first-line pasireotide has the potential to achieve substantial tumor volume reduction in addition to significant improvements in cortisol levels and signs and symptoms in patients with Cushing's disease for whom surgery is not an option.

Clinical improvement of a toddler with COVID-19 focal cerebral arteriopathy possibly due to intra-arterial nimodipine.

Pediatric stroke is considered an infrequent complication of COVID-19. Focal cerebral arteriopathy (FCA) is one of the most common causes of arterial ischemic stroke in a previously healthy child. The present report describes a toddler with FCA most likely induced by SARS-CoV-2 infection who showed significant clinical improvement that may be related to injection of intra-arterial nimodipine. To our knowledge, this is the first reported use of nimodipine in this setting.

Osimertinib in advanced EGFR-mutant lung adenocarcinoma with asymptomatic brain metastases: an open-label, 3-arm, phase II pilot study.

BACKGROUND: Osimertinib is selective for both epidermal growth factor receptor (EGFR)-tyrosine-kinase inhibitor (TKI) sensitizing and Thr790Met mutations. While intracranial activity of osimertinib is documented in larger trials, a prospective study focusing exclusively on patients with asymptomatic brain metastases has not been reported. METHODS: In this nonrandomized, phase II, open-label, 3-arm prospective proof-of-concept pilot study, 48 patients with metastatic EGFR-mutant lung adenocarcinoma (LUAD) received osimertinib 80 mg daily. Patients were either treatment naive (arm A = 20) or previously treated with an EGFR-TKI and Thr790Met positive (arm B = 18) or negative (arm C = 10). In cases of isolated intracranial progression, osimertinib dose was escalated (160 mg). The primary endpoints were intracranial objective response rate (iORR) and intracranial disease control rate (iDCR). The secondary endpoint was intracranial progression-free survival (iPFS). This study is registered at Clinicaltrials.gov, NCT02736513. RESULTS: The iORRs were 84.2%, 66.7%, and 50% and the iDCRs were 94.7%, 94.4%, and 80% in arms A, B, and C, respectively. The median iPFS was 11.8 months (95% CI 7.7 to NA), 7.6 months (95% CI 5.3 to NA), and 6.3 months (95% CI 3.9 to NA) in arms A, B, and C, respectively. Following dose escalation, pooled iORR was 54% (arm A = 5, arm B = 4, arm C = 2). Adverse events were similar to those in previously published literature. CONCLUSION: Osimertinib demonstrated high efficacy on brain metastases. All trial arms displayed a significant decrease in the number and diameter of target lesions. These findings indicate that osimertinib is effective for Thr790Met-positive and -negative LUAD patients with asymptomatic brain metastases. Therefore, osimertinib should be considered a viable option for EGFR-mutant patients with brain involvement regardless of their Thr790Met mutation status.

Vocal cord paresis on CTA - A novel tool for the diagnosis of lateral medullary syndrome.

BACKGROUND: Diagnosis of lateral medullary syndrome (LMS) is often delayed due to elusive clinical presentations and frequently non-revealing neuroimaging tests. We aimed to investigate the use of ipsilateral vocal cord paresis (VCP) identified on neck computed tomography angiography (CTA) as an early diagnostic sign for LMS. METHODS: Medical records were queried for patients admitted with LMS between 1/2012 and 10/2020. A control group of patients undergoing CTA for transient or no neurological symptoms was matched for sex and age. Clinical data were collected by a stroke neurologist. Two neuroradiologists independently and blindly assessed CTA images for radiological signs of VCP. RESULTS: Fifteen LMS and 15 control patients were included in the analysis. Median time from arrival to LMS diagnosis was 29.4 h [IQR 7,47] and twice as long in patients who suffered aspiration pneumonia. Thrombolysis rate was 0% in LMS patients versus 14.5% in general stroke patients. Dysphonia was noted in the emergency department in three (20%) patients, whereas all 15 patients had radiological signs of VCP on CTA. Medialization of a true vocal cord was the most sensitive (100%) and specific (80-87%) sign for LMS, with good inter-rater agreement (kappa 0.66). Timely detection of VCP on CTA could have shortened median time to LMS diagnosis by 14 h and enabled thrombolytic therapy in 3 (20%) patients. CONCLUSIONS: VCP on CTA is a valuable sign for the diagnosis of LMS. If detected early, it may enable reperfusion therapy and prevent aspiration pneumonia, consequently saving life and diminishing disability.

Cardiomyopathy associated with Ceutzfeld-Jakob disease: a diagnosis of exclusion: a case report.

BACKGROUND: Creutzfeldt-Jakob disease (CJD), the most common prion disease in humans, is primarily known for its adverse neurological impact and inevitable mortality. Data regarding myocardial involvement in CJD are scarce. CASE SUMMARY: A 54-year-old female patient, presented with progressive effort dyspnoea, was diagnosed with unexplained non-ischaemic cardiomyopathy. An extensive cardiac work-up including cardiac magnetic resonance imaging (MRI) did not reveal any underlying aetiology. Simultaneously, the patient developed involuntary limb movements and progressive cognitive decline. Thalamic high-signal abnormalities on diffusion-weighted images were apparent on brain MRI. Based on these findings, she was subsequently referred to a neurology department, where she suddenly died the day after her admission. Brain autopsy demonstrated spongiform encephalopathy. A genetic analysis performed to her son revealed a mutation in the PRNP gene; all of these were consistent with CJD. DISCUSSION: This case describes the clinical association of CJD and cardiomyopathy and the diagnosis prion-induced cardiomyopathy by exclusion. It is not inconceivable that the coexistence of these two clinical entities may be related to genetic expression and contemporaneously deposition of infectious prions in myocardial muscle and brain tissue. Awareness of this possible association could be of important public-safety concern, and merits further collaborative cardiac-neurological work-up to elucidate this phenotype among patients with unexplained cardiomyopathy with neurological symptoms that resemble CJD.

The Utility of Early Postoperative Neuroimaging in Elective/Semielective Craniotomy Patients: A Single-Arm Prospective Trial.

BACKGROUND: The necessity and timing of early postoperative imaging (POI) are debated in many studies. Despite the consensus that early POI does not change patient management, these examinations are routinely performed. This is the first prospective study related to POI. Our aims were to assess the necessity of early POI in asymptomatic patients and to verify accuracy of the presented algorithm. METHODS: This was an algorithm-based prospective single-center study. The algorithm addressed preoperative, perioperative, and postoperative considerations, including estimated pathology type, device placement, and postoperative neurologic change. Early computed tomography scans were obtained in all patients, but if postoperative algorithm indications did not recommend a scan, the treating team was blinded to them, and patient management was conducted based on clinical examinations alone. A neuroradiologist and study-independent neurosurgeon reviewed all the scans. RESULTS: Of 103 enrolled patients, 88 remained asymptomatic, and 15 experienced symptoms postoperatively. Pathology was present on POI in 1% of the asymptomatic patients and 53% of the symptomatic patients (P < 0.001). In the asymptomatic group, no treatment modifications were made postoperatively. Blinding of the surgical team was not removed, and 20% of the symptomatic patients returned to the operating room because of imaging and neurologic findings. The goal of <5% algorithm failure was reached with statistical significance. CONCLUSIONS: In asymptomatic postoperative patients in whom early imaging is not performed for oncologic indications, device placement verification, or similar reasons, POI is unnecessary and does not change the management of these patients.

Paraneoplastic cerebellar degeneration mimicking acute post-infectious cerebellitis.

Acute cerebellitis is a monophasic non-progressive encephalitis restricted to the cerebellum, while paraneoplastic cerebellar degeneration is a subacute progressive disorder, which may either accompany or herald Hodgkin's disease. In the present report, we describe a young man with clinical and laboratory features of acute post-infectious cerebellitis in whom the progressive relapsing course subsequently led to the diagnosis of Hodgkin's disease. Dynamic changes observed on repeated MRIs during the protracted clinical course imply the presence of early active inflammation and subsequent neuronal atrophy.

High incidence of silent cerebral infarcts in adult patients with beta thalassemia major.

OBJECTIVES: Survival of beta thalassemia major (TM) patients has improved significantly over the past few decades. Consequently, less commonly reported complications are now being recognized. An incidence as high as 60% of silent cerebral infarcts (SCI) has been demonstrated by brain Magnetic Resonance Imaging (MRI) studies in beta thalassemia intermedia (TI). The aim of this study was to determine whether regularly transfused TM adult patients experience less SCI, as compared to the incidence described in TI. METHODS: In this observational study, 28 transfusion dependent TM patients, >18years of age underwent brain MRI studies. RESULTS: Focal bright foci in the cerebral white matter were demonstrated in 17 (60.7%) patients; most of them had multiple lesions. Elevated serum ferritin (SF), primarily 5years Area Under the Curve, was found to have a significant association with the presence of SCI (p<0.031). Similar results were found when 4 patients with intact spleen and 2 patients with splenules were excluded (p=0.027). There was no significant association between number of SCI and clinical or other laboratory parameter evaluated. CONCLUSIONS: The present study demonstrates a high rate of SCI in regularly transfused TM adult patients. Effective continuous iron chelation, preventive low dose aspirin and routine periodical brain MRI are recommended.

Primary brain T-cell lymphoma in an HTLV-1 serologically positive male.

Primary central nervous system lymphoma (PCNSL) is a subgroup of extranodal non-Hodgkin lymphoma usually due to B-cells. The incidence of T-cell PCNSL is 1-4% in Western countries. Human T-lymphotropic virus (HTLV-1) causes tropical spastic paraparesis/myelopathy and adult T-cell leukemia/lymphoma. We describe the extremely rare occurrence of T-cell PCNSL in a 29 year old HTLV-1 carrier. Additional unusual features of the case included the patient's young age and normal cerebrospinal fluid cytological findings, without leptomeningeal spread. Given the long latency between HTLV-1 infection and disease manifestation, more such cases may be diagnosed in the future. We recommend that every patient with T-cell PCNSL be screened for HTLV-1.