Lung cancer is associated with acute ongoing cerebral ischemia: A population-based study.

BACKGROUND AND OBJECTIVES: Cerebral microinfarcts (CMIs) are the most common type of brain ischemia; however, they are extremely rare in the general population. CMIs can be detected by magnetic resonance diffusion-weighted imaging (MRI-DWI) only for a very short period of approximately 2 weeks after their formation and are associated with an increased stroke risk and cognitive impairment. We aimed to examine CMI detection rate in patients with lung cancer (LC), which is strongly associated with ischemic stroke risk relative to other cancer types. METHODS: We used the Clalit Health Services record (representing more than 5 million patients) to identify adults with LC and breast, pancreatic, or colon cancer (non-lung cancer, NLC) who underwent brain magnetic resonance diffusion (MRI) scan within 5 years following cancer diagnosis. All brain MRI scans were reviewed, and CMIs were documented, as well as cardiovascular risk factors. RESULTS: Our cohort contained a total of 2056 MRI scans of LC patients and 1598 of NLC patients. A total of 143 CMI were found in 73/2056 (3.5%) MRI scans of LC group compared to a total of 29 CMI in 22/1598 (1.4%) MRI scans of NLC (p < 0.01). Cancer type (e.g. LC vs NLC) was the only associated factor with CMI incidence on multivariate analysis. After calculating accumulated risk, we found an incidence of 2.5 CMI per year in LC patients and 0.5 in NLC. DISCUSSION: CMIs are common findings in cancer patients, especially in LC patients and therefore might serve as a marker for occult brain ischemia, cognitive decline, and cancer-related stroke (CRS) risk.

Association of Acute Incidental Cerebral Microinfarcts With Subsequent Ischemic Stroke in Patients With Cancer: A Population-Based Study.

BACKGROUND AND OBJECTIVES: Incidental diffuse-weighted imaging (DWI)-positive subcortical and cortical lesions, or acute incidental cerebral microinfarcts (CMIs), are a common type of brain ischemia, which can be detected on magnetic resonance DWI for approximately 2 weeks after occurrence. Acute incidental CMI was found to be more common in patients with cancer. Whether acute incidental CMI predicts future ischemic stroke is still unknown. We aimed to examine the association between acute incidental CMI in patients with cancer and subsequent ischemic stroke or transient ischemic attack (TIA). METHODS: This is a retrospective cohort study. We used Clalit Health Services records, representing over half of the Israeli population, to identify adults with lung, breast, pancreatic, or colon cancer who underwent brain MRI between January 2014 and April 2020. We included patients who underwent scan between 1 year before cancer diagnosis and 1 year after diagnosis. Primary outcome was ischemic stroke or TIA using International Classification of Diseases, Ninth Revision codes. Secondary outcomes were intracranial hemorrhage (ICH) and mortality. Records were followed from first MRI until primary outcome, death, or end of follow-up (January 2023). Cox proportional hazards models were used to calculate hazard ratio (HR) for patients with and without acute incidental CMI, as a time-dependent covariate. RESULTS: The study cohort included 1,618 patients with cancer, among whom, 59 (3.6%) had acute incidental CMI on at least 1 brain MRI. The median (interquartile range) time from acute incidental CMI to stroke or TIA was 26 days (14-84). On multivariable analysis, patients with acute incidental CMI had a higher stroke or TIA risk (HR 2.97, 95% CI 1.08-8.18, p = 0.035) compared with their non-CMI counterparts. Acute incidental CMIs were also associated with mortality after multivariable analysis (HR 2.76, 95% CI 2.06-3.71, p < 0.001); no association with ICH was found. DISCUSSION: Acute incidental CMI on brain MRI in patients with active cancer is associated with an increased risk of near-future ischemic stroke or TIA and mortality. This finding might suggest that randomly detected acute incidental CMI in patients with cancer may guide primary cerebrovascular risk prevention and etiologic workup.

Cognitive decline after stroke: relation to inflammatory biomarkers and hippocampal volume.

BACKGROUND AND PURPOSE: Inflammation may contribute to cognitive impairment after stroke. Inflammatory markers are associated with hippocampal atrophy. We tested whether markers of inflammation, erythrocyte sedimentation rate (ESR), and serum levels of C-reactive protein are associated with reduced hippocampal volume and poor cognitive performance among stroke survivors. METHODS: We analyzed 368 consecutive cases from our prospective study of first-ever mild-moderate stroke patients. MRI, cognitive tests, and inflammatory markers were determined. Patients were reevaluated 6 and 12 months after the event. RESULTS: ESR remained unchanged in follow-up examinations, suggesting a chronic inflammation background in some patients. Higher levels of C-reactive protein and ESR were associated with worse performance in cognitive tests, particularly memory scores. This association was maintained for ESR (but not C-reactive protein) after adjustment for confounders (P=0.002). Patients with smaller hippocampi had inferior cognitive results. Moreover, in a multivariate regression model, higher ESR values (but not C-reactive protein) were related to reduced hippocampal volume (P=0.049). CONCLUSIONS: This report shows a strong relationship between ESR and hippocampal volume, as well as with cognitive performance among poststroke patients. This could plausibly relate to incipient cognitive decline via hippocampal pathways.

Safety of lumbar puncture for people who are treated with ADP receptor antagonists.

BACKGROUND: Current guidelines state that clopidogrel and other adenosine-diphosphate receptor antagonists (ADPra) should be stopped for at least 7 days before lumbar puncture (LP). This practice may delay the diagnosis of treatable neurological emergencies and may increase the risk of cardiovascular morbidity due to withholding antiplatelets. We aimed to summarize all cases under our care, in which LP was performed without discontinued ADPra. METHODS: A retrospective case series study of all patients who underwent LP without interruption of ADPRa or with treatment interruption that was shorter than 7 days. Medical records were searched for documented complications. Traumatic tap was defined as cerebrospinal fluid red cell count ≥ 1000 cell/µL. Incidence of traumatic tap among people who underwent LP under ADPRa was compared to traumatic tap incidence in two control groups: LP under aspirin and LP without any anti-platelet. RESULTS: 159 patients underwent LP under ADPRa [Age: 68.4 ± 12.1, Female: 63 (40%), 81 (51%) were treated with both aspirin and ADPRa]. 116 procedures were carried out without any interruption of ADPRa. In the other 43, the median delay between treatment interruption and the procedure was 2 days (range: 1-6 days). Incidence of traumatic tap was 8/159 (5%), 9/159 (5.7%) and 4/160 (2.5%) among those who underwent LP under ADPRa, under aspirin and without any anti-platelet, respectively. [X2(2) = 2.13, P = 0.35)]. No patient developed spinal hematoma or any neurological deficit. CONCLUSIONS: Lumbar puncture without discontinuation of ADP receptor antagonists seems safe. Similar case series may ultimately lead to guidelines change.

Risk of breakthrough COVID-19 after vaccination among people with multiple sclerosis on disease-modifying therapies.

BACKGROUND: Disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) may decrease vaccine effectiveness. We aimed to explore the association between various DMTs and the risk for breakthrough COVID-19. METHODS: Population-based data from Clalit Health Services, Israel's largest healthcare organization, were used. PwMS treated with DMTs without prior COVID-19 were followed from the commencement of the mass vaccination campaign in December 2020. The end of follow-up was at the time of COVID-19 infection, the receipt of a third vaccine dose or until the end of August 2021. Time-dependent multivariate Cox proportional hazard models were used to estimate hazard ratios for COVID-19 according to vaccination, DMT, age, gender, disability and comorbidities. RESULTS: 2511 PwMS treated with DMTs were included (Age: 46.2 ± 14.6, 70% Female, EDSS: 3.0 ± 2.1). Of whom, 2123 (84.5%) received 2 vaccine doses. On multivariate models that included all pwMS, vaccination was protective (HR = 0.41, P < 0.001). On multivariate models that included only fully vaccinated pwMS cladribine, ocrelizumab, S1P receptor modulators and natalizumab were associated with breakthrough COVID-19 (HR = 6.1, 4.7, 3.7 and 3.3; P = 0.004, 0.008, 0.02 and 0.05, respectively). On multivariate models that included unvaccinated and fully vaccinated pwMS on each DMT separately, a protective trend was noted for vaccination on all DMTs (0.09 < HR < 0.65), except for cladribine (HR = 1.1). This protective trend was not statistically significant on ocrelizumab, S1P receptor modulators and natalizumab. COVID-19 among pwMS was generally mild. Only 2 vaccinated pwMS had a severe infection with eventual recovery. CONCLUSIONS: Vaccination effectively protects pwMS from COVID-19. An increased risk of breakthrough infection was noted on high-efficacy DMTs, however COVID-19 after vaccination was usually mild.

Association Between Guillain-Barré Syndrome and COVID-19 Infection and Vaccination: A Population-Based Nested Case-Control Study.

BACKGROUND AND OBJECTIVES: Existing data regarding occurrence of Guillain-Barré syndrome (GBS) after coronavirus disease 2019 (COVID-19) infection and vaccination are inconclusive. We aimed to assess the association between GBS and both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 vaccine. METHODS: We conducted a nested case-control study in a cohort of 3,193,951 patients aged 16 years or older, without a diagnosis of prior GBS, from the largest health care provider in Israel. Participants were followed from January 1, 2021, until June 30, 2022, for the occurrence of GBS. Ten randomly selected controls were matched to each case of GBS on age and sex. We assessed both SARS-CoV-2 infection and COVID-19 vaccine administration in the prior 6 weeks in cases and controls. RESULTS: Overall, 76 patients were diagnosed with GBS during follow-up and were matched to 760 controls. A positive test for SARS-CoV-2 was detected in 9 (11.8%) cases and 18 (2.4%) controls. An administration of COVID-19 vaccine was detected in 8 (10.5%) cases (all Pfizer-BioNTech [BNT162b2] vaccine) and 136 (17.9%) controls (134 Pfizer-BioNTech vaccine). Multivariable conditional logistic regression models showed that the odds ratio for GBS associated with SARS-CoV-2 infection and COVID-19 vaccine administration was 6.30 (95% CI 2.55-15.56) and 0.41 (95% CI 0.17-0.96), respectively. The results were similar when exposure to SARS-CoV-2 infection or COVID-19 vaccine administration was ascertained in the prior 4 and 8 weeks, although did not reach statistical significance for COVID-19 vaccine at 4 weeks. DISCUSSION: Our study suggests that SARS-CoV-2 infection is associated with increased risk of GBS, whereas Pfizer-BioNTech COVID-19 vaccine is associated with decreased risk of GBS.

Prevalence and Significance of Unrecognized Renal Dysfunction in Patients with Stroke.

BACKGROUND: Unrecognized renal dysfunction, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m(2) in the presence of normal serum creatinine levels, is a common comorbidity among patients with various cardiovascular conditions. The current study was aimed to evaluate the prevalence and clinical significance of unrecognized renal dysfunction in patients with acute stroke. METHODS: The cohort consisted of patients with acute stroke included in the prospective National Acute Stroke ISraeli (NASIS) registry. Unrecognized renal insufficiency was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m(2) in the presence of serum creatinine ≤1.2 mg/dL. The 2 primary outcomes were in-hospital mortality and the composite of in-hospital mortality or severe disability at hospital discharge. RESULTS: Of the 7900 patients with stroke included in the study, 5571 (70.5%) had normal renal function, 1510 (19.1%) had recognized renal insufficiency, and 819 (10.4%) had unrecognized renal insufficiency. Mortality rates were higher in patients with recognized and unrecognized renal insufficiency compared with patients with normal renal function (9.9%, 9.1%, and 4.4%, respectively, P < .0001). Adjusted odds ratios (ORs) for in-hospital mortality were higher for patients with renal dysfunction recognized (OR, 2.1; 95% confidence interval [CI], 1.6-2.7; P < .001) or unrecognized (OR, 1.6; 95% CI, 1.1-2.2; P = .006) compared with patients with normal renal function. Likewise, adjusted ORs for the composite of in-hospital mortality or severe disability at hospital discharge were higher for patients with renal dysfunction recognized (OR, 1.3; 95% CI, 1.1-1.5; P = .004) or unrecognized (OR, 1.2; 95% CI, 1.01-1.5; P = .04). CONCLUSIONS: Unrecognized renal insufficiency is common among patients with acute stroke and is associated with adverse short-term outcomes.

Predicting the need for hospital admission of TIA patients.

BACKGROUND: It is unknown which patient will benefit most from hospital admission after transient ischemic attack (TIA). Our aim was to define predictors of a positive hospital outcome. METHODS: We used two cohorts of TIA patients: the University of Texas at Houston Stroke Center (UTH); and Tel-Aviv Sourasky Medical Center in Israel (TASMC) for external validation. We retrospectively reviewed medical records and imaging data. We defined positive yield (PY) of the hospital admission as identification of stroke etiologies that profoundly changes clinical management. RESULTS: The UTH cohort included 178 patients. 24.7% had PY. In the multivariate analysis, the following were associated with PY: coronary disease (CAD); age; and acute infarct on DWI. We then derived a composite score termed the PY score to predict PY. One point is scored for: age>60, CAD, and acute infarct on DWI. The proportion of PY by PY score was as follows: 0-6%; 1-22%; 2-47%; 3-67% (p<0.001). In the validation cohort PY score was highly predictive of PY and performed in a very similar manner. CONCLUSIONS: Our data suggest, the PY score may enable physicians to make better admission decisions and result in better, safer and more economical care for TIA patients.