Absence Of Neurological Symptoms Research Articles

Distinctive Pattern of Metal Deposition in Neurologic Wilson Disease: Insights From 7T Susceptibility-Weighted Imaging.

Noninvasive and accurate biomarkers of neurologic Wilson disease (NWD), a rare inherited disorder, could reduce diagnostic error or delay. Excessive subcortical metal deposition seen on susceptibility imaging has suggested a characteristic pattern in NWD. With submillimeter spatial resolution and increased contrast, 7T susceptibility-weighted imaging (SWI) may enable better visualization of metal deposition in NWD. In this study, we sought to identify a distinctive metal deposition pattern in NWD using 7T SWI and investigate its diagnostic value and underlying pathophysiologic mechanism. Patients with WD, healthy participants with monoallelic ATP7B variant(s) on a single chromosome, and health controls (HCs) were recruited. NWD and non-NWD (nNWD) were defined according to the presence or absence of neurologic symptoms during investigation. Patients with other diseases with comparable clinical or imaging manifestations, including early-onset Parkinson disease (EOPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and neurodegeneration with brain iron accumulation (NBIA), were additionally recruited and assessed for exploratory comparative analysis. All participants underwent 7T T1, T2, and high-resolution SWI scanning. Quantitative susceptibility mapping and principal component analysis were performed to illustrate metal distribution. We identified a linear signal intensity change consisting of a hyperintense strip at the lateral border of the globus pallidus in patients with NWD. We termed this feature "hyperintense globus pallidus rim sign." This feature was detected in 38 of 41 patients with NWD and was negative in all 31 nNWD patients, 15 patients with EOPD, 30 patients with MSA, 15 patients with PSP, and 12 patients with NBIA; 22 monoallelic ATP7B variant carriers; and 41 HC. Its sensitivity to differentiate between NWD and HC was 92.7%, and specificity was 100%. Severity of the hyperintense globus pallidus rim sign measured by a semiquantitative scale was positively correlated with neurologic severity (ρ = 0.682, 95% CI 0.467-0.821, p < 0.001). Patients with NWD showed increased susceptibility in the lenticular nucleus with high regional weights in the lateral globus pallidus and medial putamen. The hyperintense globus pallidus rim sign showed high sensitivity and excellent specificity for diagnosis and differential diagnosis of NWD. It is related to a special metal deposition pattern in the lenticular nucleus in NWD and can be considered as a novel neuroimaging biomarker of NWD. The study provides Class II evidence that the hyperintense globus pallidus rim sign on 7T SWI MRI can accurately diagnose neurologic WD.

Abstract 4798: MRI screening for brain metastases (BrM) versus SYMptom-directed brain imaging for patients with triple negative (TN) or HER2+ metastatic breast cancer (MBC): An ad-hoc interim analysis of a randomized phase II pilot study

Abstract Background: Patients with HER2+ or TN MBC are at high risk of developing BrM, but the role of MRI screening for early detection of asymptomatic BrM has not yet been established. Methods: We conducted a multicentre phase II pilot study, which randomized patients with TN or HER2+ MBC to 1 year of BrM screening (contrast enhanced brain MRI at baseline, 4, 8, and 12 months) versus a control arm of symptom directed brain imaging (MRI only if symptoms of BrM develop). The primary goal was to determine the feasibility of a future randomized trial of BrM screening versus symptom-directed imaging in this patient population. Key inclusion criteria were age ≥18; TN MBC diagnosed ≤12 weeks prior to study entry or HER2+ MBC with no restrictions regarding time of diagnosis; no symptoms of BrM or known asymptomatic BrM; ECOG ≥ 1 and no MRI contraindications. Overall (EORTC QLQ BN20) and neurologic-specific (FACT-BR tools) quality-of-life as well as cancer-related anxiety (NCI PRO-CTCAE) were assessed at baseline, 6 and 15 months. Criteria rendering a future trial “not feasible” were defined a-priori as: &amp;lt;30% of eligible patients enroll in the study, &amp;lt;50% complete the study protocol, and/or &amp;gt;50% of patients allocated to the control arm during the 1 year study period are screened for asymptomatic BrM with CT or MRI. Results: Between 2018 and 2023, 44 patients from 3 participating centres enrolled in the study. Thirty-five participants (80%) had HER2+ and 9 (20%) had TN MBC. Of the 22 patients randomized to each of the study arms; 3 patients (8%) in each arm withdrew prior to study completion. Reasons for withdrawal included claustrophobia (n=3) or discontent with their randomised arm (n=3) or follow-up requirements (n=1). Metrics regarding the proportion of eligible patients who enrolled in the study were only collected from the Sunnybrook Odette Cancer Centre site; of 91 patients approached, 38 (42%) enrolled in the study. Within the 12-month study period, the incidence of BrM among patients in the screening arm was n=3 (14%) versus n=4 (18%) in the control arm. To-date among patients in the study arm, 11 (50%) completed the 12-month screening protocol, 5 (23%) remain on study and 6 (27%) did not complete the protocol due to either death or early study withdrawal. Among patients in the control arm, 10 (45%) completed 12-month follow-up, 4 (18%) remain on study and 8 (36%) did not complete follow-up due to either death or early study withdrawal. In total, 13 patients (59%) in the control arm had brain imaging, 4 in the absence of neurological symptoms. Conclusion: A large randomized trial to investigate the utility of MRI-based surveillance for asymptomatic detection of BrM in the proposed patient population is likely feasible, although episodic brain imaging in the control arm was common. Analysis of patient reported outcomes is ongoing. Citation Format: Katarzyna Joanna Jerzak, Megan Shum, Gregory Pond, Orit Freedman, Gursimran Chandhoke, Tatiana Conrad, Priscilla Brastianos, Gregory Stanisz, Arjun Sahgal, Ellen Warner. MRI screening for brain metastases (BrM) versus SYMptom-directed brain imaging for patients with triple negative (TN) or HER2+ metastatic breast cancer (MBC): An ad-hoc interim analysis of a randomized phase II pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4798.

Identification of incidental brain tumors in prostate cancer patients via PSMA PET/CT.

Brain metastases are rare in patients with prostate cancer and portend poor outcome. Prostate-specific membrane antigen positron emission tomography (PSMA PET)/CT scans including the brain have identified incidental tumors. We sought to identify the incidental brain tumor detection rate of PSMA PET/CT performed at initial diagnosis or in the setting of biochemical recurrence. An institutional database was queried for patients who underwent 68Ga-PSMA-11 or 18F-DCFPyL (18F-piflufolastat) PET/CT imaging at an NCI-designated Comprehensive Cancer Center from 1/2018 to 12/2022. Imaging reports and clinical courses were reviewed to identify brain lesions and describe clinical and pathologic features. Two-thousand seven hundred and sixty-three patients underwent 3363 PSMA PET/CT scans in the absence of neurologic symptoms. Forty-four brain lesions were identified, including 33 PSMA-avid lesions: 10 intraparenchymal metastases (30%), 4 dural-based metastases (12%), 16 meningiomas (48%), 2 pituitary macroadenomas (6%), and 1 epidermal inclusion cyst (3%) (incidences of 0.36, 0.14, 0.58, 0.07, and 0.04%). The mean parenchymal metastasis diameter and mean SUVmax were 1.99cm (95%CI:1.25-2.73) and 4.49 (95%CI:2.41-6.57), respectively. At the time of parenchymal brain metastasis detection, 57% of patients had no concurrent extracranial disease, 14% had localized prostate disease only, and 29% had extracranial metastases. Seven of 8 patients with parenchymal brain metastases remain alive at a median 8.8 months follow-up. Prostate cancer brain metastases are rare, especially in the absence of widespread metastatic disease. Nevertheless, incidentally detected brain foci of PSMA uptake may represent previously unknown prostate cancer metastases, even in small lesions and in the absence of systemic disease.

Cerebral Microembolism in Patient with COVID-19

Objective: Coronavirus-2019 (Covid-19) was first observed in December 2019 and recognized as a pandemic by the World Health Organization. Apart from respiratory symptoms, neurological, dermatological, and gastrointestinal symptoms can also occur in humans. Some neurological symptoms may be caused by microembolism. The present study aims to determine the presence of microemboli in patients with Covid-19 using Transcranial Doppler (TCD) ultrasonography and examine its correlation with D-Dimer levels. Material and Methods: This study involved 20 hospitalized patients diagnosed with Covid-19 using the Polymerase Chain Reaction (PCR) method. D-Dimer results of the patients were recorded and analyzed within two groups (First group: D-Dimer &lt; 1 mg/L, and second group: D-Dimer ≥ 1 mg/L). The middle cerebral arteries were bilaterally examined with TCD to screen for microemboli. Patients were classified into two groups based on the number of MES (first group: 0-3 MES (n=10), second group: ≥ 4 MES). Results: Cerebral arterial microemboli were observed in patients with Covid-19. The relationship between D-Dimer and emboli was investigated, and the presence of microemboli was found to be statistically significant in both the low D-Dimer value group (p &lt; 0.001) and the high D-Dimer value group (p &lt; 0.003). Furthermore, D-Dimer results were found to be higher in the group with a greater number of microemboli (p &lt; 0.001). Conclusions: Microemboli were detected in the cerebral arteries of Covid-19 patients, even in the absence of neurological symptoms. Additionally, a positive correlation was observed between high D-Dimer levels and the presence of cerebral microemboli. Therefore, physicians should assess the presence of microemboli in Covid-19 patients and determine appropriate treatment methods accordingly.

Neurological disorders in patients with thrombotic thrombocytopenic purpura

Aim: to analyze the first neurological manifestation in patient with thrombotic thrombocytopenic purpura (TTP). Material and methods. The appeals from physicians who suspected TTP were included in the study. The neurological symptoms in 40 patients with TTP were also analyzed. Results. Among 208 physician appeals about the suspicion of TTP and the referral of plasma samples for testing of ADAMTS13 activity, there were 2% of neurologists. The diagnosis of TTP was confirmed in 40 patients. 9 (22.5%) had no neurological symptoms, and 31 (77.5%) had neurological disorders. Patients with neurological symptoms were older than patients without neurological symptoms (median 37 years and 31 years, p = 0.006). Neurological symptoms were less frequently observed in pregnancy-associated TTP (p = 0.008). Among neurological symptoms there were speech disorders (40%), headache (30%), cognitive deficits (32.5%), depression of consciousness (22.5%), paresis (25%), sensation disorders (20.5%), seizures (10%). Magnetic resonance imaging/computed tomography (MRI/CT) revealed ischemic stroke in 47.5%, hemorrhagic stroke in 15%. In 6 patients, despite neurological symptoms, no pathology was detected with MRI/CT. In 4 patients, in the absence of neurological symptoms, MRI/CT revealed ischemic foci in the brain. 8 patients died: 2 patients died from sepsis, 6 - from ischemic stroke. In surviving patients, neurological symptoms regressed after remission. Conclusion. Neurological symptoms are detected in most patients with TTP. Brain MRI/CT should be performed in all patients with TTP

An outbreak of acute neurological illness associated with drinking water source following a cyclone in Eluru, West Godavari district, Andhra Pradesh, India, December 2020

BackgroundIn December 2020, over 500 residents of Eluru City were hospitalised with seizures and sudden loss of consciousness (LOC) resembling the neurotoxic effects of organochlorine poisoning after a flooding event during the last week of November 2020. We described the epidemiological investigation of outbreak and identified risk factors. MethodsWe performed descriptive analysis followed by 1:1 unmatched case-control study. Cases were identified through house-to-house search and review of medical records at district hospital. A case defined as sudden onset LOC or new-onset seizures in an Eluru resident aged ≥1 year, December 1–15, 2020 and a control as absence of neurological symptoms in a person aged ≥1 year selected randomly from same administrative division of the case. We compared cases and controls for possible risk factors and calculated adjusted odds ratio (aOR) with 95% confidence interval (CI). Biological and environmental samples were tested for contaminants. ResultsWe identified 545 cases (56% males), including one death. Seizures were reported in 491 (90%) cases. Median age was 27 years (interquartile range: 17–37 years) and 480 (88%) cases resided in urban area. Cases were clustered in administrative divisions supplied by municipal water reservoirs. Cases were more likely than controls to use municipal water as primary source of drinking water (aOR = 4.6, 95% CI = 1.6–13.0). High levels (average: 14.6 mg/l) of organochlorine compounds were detected in all municipal water samples (acceptable limit: <0.001 mg/l). ConclusionThis investigation highlights water ingestion as an exposure pathway for environmental contaminants (organochlorines) in the community after largescale flooding. We recommended strengthening safe water surveillance in natural disaster response contingency plans in Eluru.

Recurrent Benign Paroxysmal Positional Vertigo in DFNB16 Patients with Biallelic STRC Gene Deletions.

Deletions of STRC gene (DFNB16) account for 12% of isolated congenital mild to moderate hearing loss (HL). In mice, the stereocilin protein, encoded by STRC , is present in the vestibular kinocilium embedded in the otoconial membrane of the utricular macula. Despite this, effects on vestibular function have not been widely investigated. The aim of this study was to investigate the prevalence of benign paroxysmal positional vertigo (BPPV) in a cohort of DFNB16 patients. Observational descriptive epidemiological study. Single-center study, in a tertiary referral center. Older than 5 years, with a genetic diagnosis of HL related to biallelic STRC gene deletions, diagnosed between 2015 and 2021. Patients or their parents were interviewed to determine whether they had experienced vertigo or episodes of BPPV. Criteria were at least five acute episodes of rotatory vertigo, each lasting less than 1 minute, episodes triggered by changes in specific head position, and an absence of neurological symptoms. Sixty-four patients having mild (33%) to moderate (66%) HL were included. Median age was 15 years (range, 6-48 yr). Prevalence of BPPV was 39% (25 of 64). Median age of first onset was 13 years (range, 3-18 yr). This study showed recurrent BPPV and early age of onset in patients with biallelic STRC gene deletions. BPPV may be associated with the HL phenotype in patients with STRC gene deletions. It is important to inform patients and families of this potential risk such that appropriate management can be proposed.

Cranial CT is a mandatory tool to exclude asymptomatic cerebral hemorrhage in elderly patients on anticoagulation.

Traumatic brain injury (TBI) after falls causes death and disability with immense socioeconomic impact through medical and rehabilitation costs in geriatric patients. Diagnosing TBI can be challenging due to the absence of initial clinical symptoms. Misdiagnosis is particularly dangerous in patients on permanent anticoagulation because minimal trauma might result in severe intracranial hemorrhage. The aim of this study is to evaluate the diagnostic necessity of cranial computed tomography (cCT) to rule out intracranial hemorrhage, particularly in the absence of neurologic symptoms in elderly patients on permanent anticoagulation in their premedication. Retrospective cohort analysis of elderly trauma patients (≥ 65 years) admitted to the emergency department (ED) of the level-1-trauma center of the University Hospital Frankfurt from 01/2017 to 12/2019. The study included patients who suffered a ground-level fall with suspected TBI and subsequently underwent CT because of preexisting anticoagulation. A total of 227 patients met the inclusion criteria. In 17 of these patients, cCT showed intracranial hemorrhage, of which 14 were subdural hematomas (SDH). In 8 of the patients with bleeding showed no clinical symptoms, representing 5% (n = 160) of all symptom-free patients. Men and women were equally to suffer a post-traumatic hemorrhage. Patients with intracranial bleeding were hospitalized for 14.5 (±10.4) days. Acetylsalicylic acid (ASA) was the most prescribed anticoagulant in both patient cohorts-with or without intracerebral bleeding (70.6 vs. 77.1%, p = 0.539). Similarly, patients taking new oral anticoagulant (NOAC) (p = 0.748), coumarins, or other platelet inhibitors (p > 0.1) did not show an increased bleeding incidence. Acetylsalicylic acid and NOAC use are not associated with increased bleeding risk in geriatric trauma patients (≥ 65 years) after fall-related TBI. Even in asymptomatic elderly patients on anticoagulation, intracranial hemorrhage occurs in a relevant proportion after minor trauma to the head. Therefore, cCT is an obligatory tool to rule out cerebral hemorrhage in elderly patients under anticoagulation.

Elective or Urgent Carotid Endarterectomy in Symptomatic Patients: Analysis Based on the Type and Timing of Neurological Symptoms

The aim of this study was to retrospectively analyse perioperative and long-term outcomes of carotid endarterectomy (CEA) performed in symptomatic patients in a high-volume academic vascular centre, stratifying them according to the type of preoperative symptoms and the timing of surgery with respect to the indexed neurological event. From January 2014 to December 2020, 1,369 consecutive CEAs were performed at our institution. Data concerning these interventions were prospectively collected in a dedicated database including data concerning preoperative assessment, surgical details, perioperative (<30days) outcomes, and long-term outcomes. A retrospective analysis of the database was performed, and 213 interventions performed in symptomatic patients were found. We identified 2 subgroups of patients: patients with stable neurological symptoms (not recent transient ischemic attack (TIA) or stable major disabling stroke, stable group, and 157 patients) and patients with unstable neurological symptoms (recent TIA, crescendo TIAs, stroke in evolution, acute/recent minor stroke, unstable group, and 56 patients). Perioperative outcomes were analysed in terms of mortality, major neurological events, and local or systemic complications The results were compared using the χ2 test; these were also analysed on the basis of the presenting symptom (isolated TIA, crescendo TIA, stroke in evolution, acute/recent minor stroke, stabilized stroke) and the timing of the intervention relative to the onset of the symptom. Long term results were analysed using the life-table analysis and Kaplan-Meier curves in terms of survival, stroke-free survival, absence of neurological symptoms, and absence of significant restenosis. Overall, 30-day stroke and death rate were 4.2%. (3.1% vs. 7%, P=0.2). Two deaths occurred at 30days, both in the stable group (mortality 1.2%, P=0.4 compared to the unstable group), but no fatal strokes were recorded in the overall sample. No differences were found in terms of new perioperative neurological events and local complications between the 2 groups. We found a trend toward poorer perioperative results in patients operated on within 48hr from the indexed event and in patients operated on for stroke in evolution or acute/recent stroke, whereas we found a trend toward better results in favour of patients operated on between 8 and 14days (P=0.08). The median duration of follow-up was 24.8months (range 1-78); at 5years we did not find significant differences in terms of survival and stroke-free survival rates between 2 groups. In our experience, carotid surgery in symptomatic patients provided satisfactory results, particularly in patients with stable neurological status. Among unstable patients, the rate of complications significantly increases, mainly among treated in the very early (<48hr) period for stroke in evolution or acute/recent stroke. Once the perioperative risk is overcome, the results in the long-term setting are similarly good, both in stable and in unstable patients.

P46 A rare case of costovertebral arthritis in SLE

P46 A rare case of costovertebral arthritis in SLE

P11.23.B Neurological symptoms independently associate with overall survival in patients with melanoma brain metastases

Abstract Background Based on the the rising detection of asymptomatic brain metastases (BM) and the remarkable intracranial responses of targeted- and immunotherapy in specific subgroups of asymptomatic BM patients, we aimed to evaluate the clinical characteristics and prognostic value of neurological symptoms in BM from melanoma. Material and Methods 670 patients with newly diagnosed melanoma BM were identified from the Vienna Brain Metastasis Registry. We performed retrospective chart review and statistical outcome analyses. Results 370/670 (55.2%) patients presented with neurological symptoms including neurological deficits (316/370; 85.4%), signs of increased intracranial pressure (126/370; 34.1%) and epileptic seizures (53/370; 14.3%). 57.6% (80/139) of patients with BRAF mutated melanoma presented with asymptomatic BM at diagnosis. Absence of neurological symptoms at BM diagnosis was associated with a longer median overall survival after time of BM diagnosis (7 vs. 5 months; p&amp;lt; 0.001; log-rank test). In multivariate analysis with the diagnosis-specific graded prognostic assessment (DS-GPA: HR:1.4; 95% CI, 1.25-1.48; p&amp;lt;0.001) and the graded prognostic assessment for melanoma using molecular markers (Melanoma-molGPA: HR:0.8; 95% CI, 0.66 -0.92; p&amp;lt;0.001), the presence of neurological symptoms (HR 0.8; 95% CI, 0.69 -0.96; p=0.003/ HR:0.6; 95% CI, 0.59-0.72; p&amp;lt;0.001) was found to be independently associated with survival prognosis from time of BM diagnosis respectively. Conclusion: Neurological symptoms at the time of BM diagnosis are an independent and strong prognostic factor in melanoma BM patients. Our results argue for the integration of neurological symptoms into the prognostic assessment of patients with BM from melanoma.

Long-term outcomes after surgery for brainstem cavernous malformations: analysis of 46 consecutive cases.

The objective of this study was to evaluate the long-term outcomes after resection of brainstem cavernous malformations (BSCMs) and to assess the usefulness of the Lawton grading system in these cases. This retrospective study analyzed 46 consecutive patients with BSCMs operated on between July 1990 and December 2020. Outcomes at the last follow-up were defined as favorable (modified Rankin Scale [mRS] score 0-2) or unfavorable (mRS score > 2). The study cohort comprised 24 men (52%) and 22 women (48%), ranging in age from 8 to 78 years old (median 37 years). In 19 patients (41%), the preoperative mRS score was > 2. All patients had hemorrhagic BSCM. There were 12 (26%) mesencephalic, 19 (41%) pontine, 7 (15%) medullary, and 8 (17%) cerebellar peduncle lesions, with a maximal diameter ranging from 5 to 40 mm (median 15 mm). In total, 24 BSCMs (52%) had bilateral extension crossing the brainstem midline. Lawton grades of 0, I, II, III, IV, V, and VI were defined in 3 (7%), 2 (4%), 10 (22%), 11 (24%), 8 (17%), 7 (15%), and 5 (11%) cases, respectively. Total resection of BSCMs was attained in 43 patients (93%). There were no perioperative deaths. Excluding the 3 most recent cases, the length of follow-up ranged from 56 to 365 months. The majority of patients demonstrated good functional recovery, but regress of the preexisting oculomotor nerve deficit was usually incomplete. No new hemorrhagic events were noted after total resection of BSCMs. In 42 patients (91%), the mRS score at the time of last follow-up was ≤ 2 (favorable outcome), and in 18 (39%), it was 0 (absence of neurological symptoms). Forty-four patients (96%) demonstrated clinical improvement and 2 (4%) had no changes compared with the preoperative period. Multivariate analysis revealed that only lower Lawton grade had a statistically significant independent association (p = 0.0280) with favorable long-term outcome. The area under the receiver operating characteristic curve for prediction of favorable outcome with 7 available Lawton grades of BSCM was 0.93. Resection of hemorrhagic BSCMs by an experienced neurosurgeon may be performed safely and effectively, even in severely disabled patients. In the authors' experience, preexisting oculomotor nerve palsy represents the main cause of permanent postoperative neurological morbidity. The Lawton grading system effectively predicts long-term outcome after surgery.

307P Incidence of neurological symptoms in brain metastases from breast cancer and its impact on prognosis: An analysis of 968 patients with brain metastases

Considering the rising detection of asymptomatic brain metastases (BM) during screening and staging procedures over the last decades, we aimed to evaluate the incidence, clinical characteristics and the prognostic value of neurological symptoms in BM from breast cancer. Patients with newly diagnosed BM from breast cancer (BC) were identified from the Vienna Brain Metastasis Registry. Patients were grouped into the three main subtypes: hormone receptor-positive/HER2 (human epidermal growth factor receptor 2)-negative breast cancer (HR BC), HER2 overexpressing BC (HER2 BC) and triple-negative BC (TN BC). A retrospective chart review and statistical outcome analyses were performed. 968 patients with BM from breast cancer (34.4% HR BC; 28.9% HER2 BC; 21.8% TN BC; 14.9% unknown receptor status) were included in the analysis. 81.6% (790/968) of the patients presented with neurological symptoms at BM diagnosis including focal deficits (695/790;88.0%), signs of increased intracranial pressure (388/790;49.1%), epileptic seizures (126/790;15.9%) and neuropsychological symptoms (133/790;16.8%). Patients with HER2 BC (66/280;23.6%) were significantly more often diagnosed with BM in absence of neurological symptoms during screening procedures compared to HR BC (62/333;18.6%) and TN BC (31/211;14.7%; chi-square test; p=0.043). Among all BC subtypes, asymptomatic patients presented with a significant longer median overall survival (OS) from diagnosis of BM compared to symptomatic patients (p<0.05; log-rank test; HR BC 20 vs. 9 months; HER2 BC 20 vs. 11 months; TN 11 vs. 5 months). In multivariate analysis, the breast cancer-specific Graded Prognostic Assessment (Breast-GPA: HR:1.4; 95% CI, 1.27-1.49; p<0.001) and the presence of neurological symptoms (HR:1.6; 95% CI, 1.35-1.95; p<0.001) presented as independently associated with survival prognosis from time of BM diagnosis respectively. Neurological symptoms are independently associated with overall survival in patients with BM from breast cancer. Our results highlight the need to incorporate neurological symptoms into the prognostic assessment of patients with BM from breast cancer.

Mortality of early treatment for radiation-induced brain necrosis in head and neck cancer survivors: A multicentre, retrospective, registry-based cohort study

SummaryBackgroundThe evidence of early treatment for radiation-induced brain necrosis (RN) in head and neck cancer survivors remains insufficient. This study aimed to determine whether early anti-RN treatment was associated with lower mortality.MethodsIn this cohort study, we utilized data from the Study in Radiotherapy-related Nervous System Complications (NCT03908502) and Hong Kong Cancer Registry. We included consecutive patients who had received radiotherapy (RT) for head and neck cancers and had subsequently developed RN between Jan 8, 2005 and Jan 19, 2020. Patients who had tumor progression before the diagnosis of RN, underwent surgical brain necrosis lesions resection before corticosteroids and/or bevacizumab treatment, had intracranial metastases before the diagnosis of RN, lacked follow-up data, or had a follow-up period of less than three months were excluded. Individual-level data were extracted from electronic medical records of the above-mentioned registries. The primary outcome was all-cause death. The vital status of each patient was confirmed through a standardized telephone interview. We compared patients who received early treatment (initiating bevacizumab or corticosteroids treatment within three months after RN diagnosis) with patients who did not (following a “watch-and-wait” policy).FindingsOf 641 eligible patients, 451 patients (70·4%) received early treatment after RN diagnosis and 190 patients (29·6%) did not. Overall, 112 patients (17·5%) died, of whom 73 (16·2%) in the early treatment group and 39 (20·5%) in the watch-and-wait group, during a median follow-up of 3·87 years. The early treatment group showed a lower risk of all-cause death compared with the watch-and-wait group after adjusting for age, sex, absence or presence of neurological symptoms at baseline, RN lesion features on brain magnetic resonance imaging, history of stroke, prior tumor-related characteristics (TNM stage, RT dose and techniques, and chemotherapy), and the time interval from RT to RN (HR 0·48, 95%CI 0·30 to 0·77; p = 0·0027), and extensive sensitivity analyses yielded similar results. There was no significant difference in the effect of early treatment on post-RN survival among subgroups stratified by presence or absence of neurological symptoms at diagnosis (p for interaction=0·41).InterpretationAmong head and neck cancer survivors with RN, initiating treatment early after RN diagnosis is associated with a lower risk of all-cause mortality as compared with following the watch-and-wait policy, irrespective of whether patients exhibit symptoms or not. Further prospective randomised studies would be needed to validate our findings since the observational study design might lead to some potential confounding. In the absence of data from randomised trials, our study will have an important implication for clinicians regarding the optimal timing of treatment for RN, and provides the foundation and supporting data for future trials on this topic.FundingNational Natural Science Foundation of China (81925031, 81820108026, 81872549, 81801229, 82003389), the Science and Technology Program of Guangzhou (202007030001), Young Teacher Training Program of Sun Yat-sen University (20ykpy106), Key-Area Research and Development Program of Guangdong Province (2018B030340001), the National Medical Research Council Singapore Clinician Scientist Award (NMRC/CSA-INV/0027/2018, CSAINV20nov-0021), the Duke-NUS Oncology Academic Program Goh Foundation Proton Research Programme, NCCS Cancer Fund, the Kua Hong Pak Head and Neck Cancer Research Programme, and the National Research Foundation Clinical Research Programme Grant (NRF-CRP17-2017-05).

Impact of Brain MRI on the Diagnosis of Infective Endocarditis and Treatment Decisions: Systematic Review and Meta-Analysis.

BACKGROUND. Despite increasing use of brain MRI to evaluate patients with suspected infective endocarditis, the clinical impact of brain MRI in this setting has not yet been systematically reviewed. OBJECTIVE. The purpose of this study was to evaluate the frequency of brain MRI findings in patients with suspected or confirmed infective endocarditis and to determine the impact of such findings on clinical decisions. EVIDENCE ACQUISITION. A systematic search of the PubMed, Embase, and Cochrane databases was performed from January 1, 1990, to December 31, 2020, to identify original research investigations of brain MRI in patients with suspected or confirmed infective endocarditis. Study quality was assessed with QUADAS-2. Study endpoints included the frequency of brain MRI findings and the frequency of diagnostic modifications, modification of therapeutic plan, and modification of valve surgery plan resulting from MRI findings. Frequencies were pooled by means of the inverse variance method. Subgroup analysis was performed. EVIDENCE SYNTHESIS. A total of 21 studies with 2133 patients were included. Overall study quality was considered moderate. In terms of brain MRI findings, the pooled frequency of acute ischemic lesions was 61.9% (95% CI, 50.7-71.9%); of cerebral microbleeds, 52.9% (95% CI, 41.6-63.9%); hemorrhagic lesions, 24.7% (95% CI, 15.1-37.9%); abscess or meningitis, 9.5% (95% CI, 5.6-15.6%); and intracranial mycotic aneurysm, 6.2% (95% CI, 4.0-9.4%). Subgroup analysis after exclusion of three studies in which neurologic findings were the indication for all brain MRI examinations yielded similar frequencies of these findings. Six studies included results on the impact of brain MRI findings on clinical decisions. The frequencies of diagnostic modifications in two studies were 5.4% and 32.1%. The pooled frequency of therapeutic plan modification in six studies was 12.8% (95% CI, 6.5-23.7%) and of surgical plan modification in five studies was 14.2% (95% CI, 8.2-23.4%). CONCLUSION. In patients with suspected or confirmed infective endocarditis, brain MRI examinations commonly show relevant abnormalities that affect diagnostic and therapeutic clinical decisions. CLINICAL IMPACT. The findings support a potential role for screening brain MRI in the evaluation of patients with suspected or confirmed infective endocarditis, regardless of the presence or absence of neurologic symptoms.

Oncologic Outcome and Immune Responses of Radiotherapy with Anti-PD-1 Treatment for Brain Metastases Regarding Timing and Benefiting Subgroups.

Simple SummaryImmune checkpoint inhibitors (ICIs) and radiotherapy (RT) are widely used for patients with brain metastasis (BM). To evaluate markers for treatment response and find a treatment concept which has the best outcome effects, we analyzed data of 93 patients with BM from different cancer types. Predictive markers for survival were good performance status, melanoma as cancer type, low metastasis volume, normal inflammatory blood parameters, and a stereotactic radiotherapy concept with high doses. We found that the best survival outcome can be achieved with the concurrent use of RT and ICI. Concurrent treatment was particularly beneficial in patients with low inflammatory status and more and larger metastases, and when high doses cannot be administered. In concurrently treated patients, therapeutic response was often delayed compared to sequential treatment. Specific immune responses such as pseudoprogression and abscopal effects were induced by concurrent treatment and associated with prolonged survival.While immune checkpoint inhibitors (ICIs) in combination with radiotherapy (RT) are widely used for patients with brain metastasis (BM), markers that predict treatment response for combined RT and ICI (RT-ICI) and their optimal dosing and sequence for the best immunogenic effects are still under investigation. The aim of this study was to evaluate prognostic factors for therapeutic outcome and to compare effects of concurrent and non-concurrent RT-ICI. We retrospectively analyzed data of 93 patients with 319 BMs of different cancer types who received PD-1 inhibitors and RT at the University Hospital Cologne between September/2014 and November/2020. Primary study endpoints were overall survival (OS), progression-free survival (PFS), and local control (LC). We included 66.7% melanoma, 22.8% lung, and 5.5% other cancer types with a mean follow-up time of 23.8 months. Median OS time was 12.19 months. LC at 6 months was 95.3% (concurrent) vs. 69.2% (non-concurrent; p = 0.008). Univariate Cox regression analysis detected following prognostic factors for OS: neutrophil-to-lymphocyte ratio NLR favoring <3 (low; HR 2.037 (1.184–3.506), p = 0.010), lactate dehydrogenase (LDH) favoring ≤ULN (HR 1.853 (1.059–3.241), p = 0.031), absence of neurological symptoms (HR 2.114 (1.285–3.478), p = 0.003), RT concept favoring SRS (HR 1.985 (1.112–3.543), p = 0.019), RT dose favoring ≥60 Gy (HR 0.519 (0.309–0.871), p = 0.013), and prior anti-CTLA4 treatment (HR 0.498 (0.271–0.914), p = 0.024). Independent prognostic factors for OS were concurrent RT-ICI application (HR 0.539 (0.299–0.971), p = 0.024) with a median OS of 17.61 vs. 6.83 months (non-concurrent), ECOG performance status favoring 0 (HR 7.756 (1.253–6.061), p = 0.012), cancer type favoring melanoma (HR 0.516 (0.288–0.926), p = 0.026), BM volume (PTV) favoring ≤3 cm3 (HR 1.947 (1.007–3.763), p = 0.048). Subgroups with the following factors showed significantly longer OS when being treated concurrently: RT dose <60 Gy (p = 0.014), PTV > 3 cm3 (p = 0.007), other cancer types than melanoma (p = 0.006), anti-CTLA4-naïve patients (p < 0.001), low NLR (p = 0.039), steroid intake ≤4 mg (p = 0.042). Specific immune responses, such as abscopal effects (AbEs), pseudoprogression (PsP), or immune-related adverse events (IrAEs), occurred more frequently with concurrent RT-ICI and resulted in better OS. Other toxicities, including radionecrosis, were not statistically different in both groups. The concurrent application of RT and ICI, the ECOG-PS, cancer type, and PTV had an independently prognostic impact on OS. In concurrently treated patients, treatment response (LC) was delayed and specific immune responses (AbE, PsP, IrAE) occurred more frequently with longer OS rates. Our results suggest that concurrent RT-ICI application is more beneficial than sequential treatment in patients with low pretreatment inflammatory status, more and larger BMs, and with other cancer types than melanoma.

Mediterranean Diet and its Effects on Silent Brain Infarcts in a Cohort of Patients With Atrial Fibrillation

The benefits of Mediterranean Diet (MeDiet) in prevention of cardiovascular diseases (CVD) in general and ischemic stroke (IS) have been extensively studied and reported. We hypothesize that the consumption of nutrients typical of MeDiet would also reduce the rate of silent brain infarcts (SBI) among AF patients. Patients with a history of AF who scored 0 to 1 in the CHADS2 score, ⩾50 years and with absence of neurological symptoms were selected from Seville urban area using the Andalusian electronic healthcare database. A 3T brain MRI was performed to all participants. Demographic and clinical data and food-frequency questionnaire (FFQ) were collected. Of the 443 scanned patients, 66 presented SBI. Of them 52 accepted to be scheduled for a clinical visit and were included in the diet sub study and 41 controls were matched per age and sex. There were no statistically significant differences in baseline characteristics. After logistic regression analysis, we found that a higher consumption of fiber from fruit was independently associated with a lower risk of SBI, while a higher consumption of high glycemic load (GL) foods was associated with a higher risk of SBI in a population with AF. Our findings support that MeDiet could be suggested as a prevention strategy for SBI in patients with AF.

Histological and Morphometric Changes in the Femoral Nerve During Lateral Interbody Fusion of the Lumbar Spine: Experimental Study

Background. Neuropathies of the lumbar plexus trunks, in particular those of the femoral nerve, are the most common complications of lateral interbody fusion of the lumbar spine. Modeling of this surgical intervention in normal animals experimentally makes it possible to assess the degree of its trauma to the nervous structures, and to understand what is the reason for the persistence or aggravation of neurological symptoms iatrogenic injuries or the existing pathology progression. Purpose to study histological and morphometric changes in the femoral nerve in the long-term periods after the lateral interbody fusion modeling of the canine lumbar spine. Study design an experimental prospective continuous uncontrolled study. Materials and Methods. Discectomy via lateral approach was performed in 18 mongrel dogs (aged 2-3 years, mass 13.2-17.6 kg) at the level of L4-5 и L5-6, interbody titanium implants were mounted, the lumbar spine was stabilized with a wire device for external fixation within 30 days. Clinical and neurological evaluation was performed, as well as histological investigation of the femoral nerves from the side of surgical approach. Results. In the early postoperative period a temporary decrease in the femoral nerve function was observed, which was manifested by the disorder of the support function and muscle weakness of the pelvic limbs, decrease in the knee reflex, the foot support shift to the metatarsal pad. Later, until the end of the study (18 months), the general condition of all animals was satisfactory, there were no disorders of the limb support function and motor reflexes. After six months, in the femoral nerve there was 4-fold decrease in the proportion of large fast-conducting myelin fibers D10 m and 3-fold increase in that of the small ones. The mean axon diameter and myelin thickness were 62% and 53% of the norm. After 12-18 months, the dimensional characteristics of myelin fibers were restored. During the entire experiment, 4-6% of myelin fibers were reactively and destructively altered. Conclusions. The modeling of the lateral interbody fusion of the lumbar spine in normal animals experimentally demonstrated the absence of neurological symptoms after 6-18 months, which indicated low invasiveness of the surgical intervention. Nevertheless, the subclinical reactive and destructive changes in the myelin fibers of the femoral nerve revealed 6 months after the surgery indicated the need for preventive anti-neurotic therapy.

Cholesterol crystal embolism-related cerebral infarction: Magnetic resonance imaging and clinical characteristics.

Background and aimsCholesterol crystal embolism-related cerebral infarction (CCE-CI) is frequently misdiagnosed due to the lack of specific symptoms. To aid in differential diagnosis, this study comprehensively characterized the magnetic resonance imaging (MRI) and clinical manifestations of CCE-CI and compared these features to those of atherothrombotic cerebral infarction (ACI).MethodsThis single-center, retrospective, observational study was conducted at Kitasato University Hospital, Kanagawa, Japan. We identified 37 clinically or histopathologically confirmed CCE-CI cases and 110 ACI cases treated from January 2006 to May 2020. Groups were compared for mean age, sex ratio, clinical presentations, imaging manifestations, precipitating factors, comorbid conditions, medications, and smoking history.ResultsOf 37 eligible patients with CCE-CI, 10 (27.0%) received brain MRI, of which 8 (21.6%) exhibited high-intensity signals indicative of brain lesions on diffusion-weighted imaging (DWI). However, two patients with DWI lesions exhibited no detectable neurological abnormalities. Patients with CCE-CI frequently demonstrated bilateral DWI lesions involving the bilateral anterior and posterior circulation, a pattern absent in ACI (50% vs. 0%, p < 0.001). Compared to patients with ACI, CCE-CI patients also demonstrated significantly lower estimated glomerular filtration rate (p < 0.001) as well as more frequent eosinophilia (p = 0.006), atherosclerotic plaques ≥4-mm thick in the ascending aorta or proximal arch (p = 0.001), and aortic aneurysm (p < 0.001).ConclusionsPatients with CCE-CI develop multiple DWI lesions across several vascular territories, even in the absence of neurological symptoms. Comorbid aortic aneurysm may increase CCE-CI risk. These findings could help in the differential diagnosis of CCE-CI.

Herniated discs: when is surgery necessary?

In all levels of disc herniations the absolute surgical indications include deteriorating neurological deficits with myelopathy or cauda equina syndrome. However, this review summarized the relative indications for surgery in each level.In cervical disc herniation (CDH), the indications for surgery consist of six months of persisting symptoms, not responding to conservative treatment. However, high-quality studies are lacking, and a randomized controlled trial is now underway to clarify the indications.In thoracic disc herniation (TDH), the indications for surgery comprise failure of conservative measures and/or worsening neurological symptoms. Moreover, giant calcified thoracic disc herniations or myelopathy signs on magnetic resonance imaging, even in the absence of neurological symptoms, may benefit from surgical treatment as a preventive measure.In lumbar disc herniation (LDH), the indications for surgery include imaging confirmation of LDH, consistent with clinical findings, and failure to improve after six weeks of conservative care.Cite this article: EFORT Open Rev 2021;6:526-530. DOI: 10.1302/2058-5241.6.210020