Cluster headache: an update on clinical features, epidemiology, pathophysiology, diagnosis, and treatment.

Cluster headache (CH) is one of the worst primary headaches that remain underdiagnosed and inappropriately treated. There are recent advances in the understanding of this disease and available treatments. This paper aims to review CH's recent clinical and pathophysiological findings, diagnosis, and treatment. We performed a narrative literature review on the socio-demographics, clinical presentations, pathophysiological findings, and diagnosis and treatment of CH. CH affects 0.1% of the population with an incidence of 2.07-9.8/100,00 person-years-habitants, a mean prevalence of 53/100,000 inhabitants (3-150/100,000 inhabitants). The male-to-female ratio remains inconclusive, as the ratio of 4.3:1 has recently been modified to 1.3-2.6, possibly due to previous misdiagnosis in women. Episodic presentation is the most frequent (80%). It is a polygenetic and multifactorial entity that involves dysfunction of the trigeminovascular system, the trigeminal autonomic reflex, and the hypothalamic networks. An MRI of the brain is mandatory to exclude secondary etiologies. There are effective and safe pharmacological treatments oxygen, sphenopalatine, and great occipital nerve block, with the heterogeneity of clinical trial designs for patients with CH divided into acute, transitional, or bridge treatment (prednisone) and preventive interventions. In conclusion, CH remains underdiagnosed, mainly due to a lack of awareness within the medical community, frequently causing a long delay in reaching a final diagnosis. Recent advances in understanding the principal risk factors and underlying pathophysiology exist. There are new therapeutic possibilities that are effective for CH. Indeed, a better understanding of this challenging pathology will continue to be a subject of research, study, and discoveries in its diagnostic and therapeutic approach.

Complete remission with histamine blocker in a patient with intractable hyperadrenergic postural orthostatic tachycardia syndrome secondary to long coronavirus disease syndrome.

The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has emerged as a global public health concern and its sequels have barely started to outcrop. A good percentage of patients who suffered from COVID-19 are prone to develop long-COVID or post-COVID condition (PCC), a multisystemic, heterogeneous, chronic disorder. Patients with PCC may experience diverse manifestations, of which cardiovascular and neurological symptoms are among the most frequently reported. Indeed, dysautonomia presented as orthostatic intolerance has gained room following recent reports linking postural orthostatic tachycardia syndrome (POTS) with PCC. Disturbances in heart rate (HR) and blood pressure (BP) during postural changes are the cornerstones of orthostatic intolerance seen in patients suffering from PCC. A subtype of POTS, hyperadrenergic POTS, has been widely studied because of its association with mast cell activation syndrome (MCAS). Although a causative relationship between PCC, hyperadrenergic POTS, and MCAS remains unrevealed, these syndromes can overlap. We want to propose here a correlation produced by a close-loop mechanism with positive feedback established after SARS-CoV-2 infection in a previously healthy young patient.

Cluster headache: state of the art in treatment.

Cluster headache (CH) is the most common and devastating autonomic headache with multiple and recent advances in treatment. However, it usually goes unrecognized and is found to have a delayed and inappropriate treatment. This paper aims to review the current therapeutic options for patients with CH. We conducted a narrative literature review on the treatments available for this condition using the American Academy of Neurology (AAN) classification of therapeutic evidence. We found effective and safe pharmacological and non-pharmacological therapies with heterogeneity of clinical trial designs for patients with CH, and they are divided into three phases, namely, transitional, acute, and preventive interventions. Prednisone (A) is the most studied treatment in the transitional phase; acute attacks are treated using triptans (A), oxygen (A), and non-invasive transcutaneous vagal nerve stimulation (A). Verapamil (A) and monoclonal antibodies (possible A) are considered the first options in preventive treatments, followed by multiple pharmacological and non-pharmacological options in prophylactic treatments. In conclusion, numerous effective and safe treatments are available in treating patients with episodic, chronic, and pharmacoresistant CH according to the clinical profile of each patient.

Unveiling the Burden of Miscoding and Misclassification in Stroke Mortality: Analysis of Multiple Cause-of-Death Data in Mexico.

BACKGROUND: The prevalence of risk factors for cerebrovascular diseases in Mexico is increasing although stroke mortality declined from 1990 to 2010, without meaningful changes afterward. While improving access to adequate prevention and care could explain this trend, miscoding and misclassification in death certificates need to be assessed to unveil the true burden of stroke in Mexico. Practices in death certification along with the presence of multi-morbidity could contribute to this distortion. Analyses of multiple causes of death could reveal ill-defined stroke deaths, providing a glimpse of this bias. METHODS: Cause-of-death information from 4,262,666 death certificates in Mexico from 2009 to 2015, was examined to determine the extent of miscoding and misclassification on the true burden of stroke. Age-standardized mortality rates per 100,000 inhabitants (ASMR) were calculated for stroke as underlying and multiple causes of death, by sex and state. Deaths were classified following international standards as ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and unspecified, which were kept as an independent category to measure miscoding. To approximate misclassification, we compared ASMR under three misclassification scenarios: (1) current (the status quo); (2) moderate, which includes deaths from selected causes mentioning stroke; and (3) high which includes all deaths mentioning stroke. National and subnational data were analyzed to search for geographical patterns. RESULTS: The burden of stroke in Mexico is underreported due to miscoding and misclassification. Miscoding is an important issue since almost 60% of all stroke deaths are registered as unspecified. Multiple cause analysis indicates that stroke ASMR could increase 39.9%-52.9% of the current ASMR under moderate and high misclassification scenarios, respectively. Both problems indicate the need to improve death codification procedures and cause-of-death classification. CONCLUSIONS: Miscoding and misclassification lead to underestimation of the burden of stroke in Mexico. Stroke deaths are underreported when other important causes coexist, being diabetes the most frequent.

RNA-binding proteins as a common ground for neurodegeneration and inflammation in amyotrophic lateral sclerosis and multiple sclerosis.

The neurodegenerative and inflammatory illnesses of amyotrophic lateral sclerosis and multiple sclerosis were once thought to be completely distinct entities that did not share any remarkable features, but new research is beginning to reveal more information about their similarities and differences. Here, we review some of the pathophysiological features of both diseases and their experimental models: RNA-binding proteins, energy balance, protein transportation, and protein degradation at the molecular level. We make a thorough analysis on TDP-43 and hnRNP A1 dysfunction, as a possible common ground in both pathologies, establishing a potential link between neurodegeneration and pathological immunity. Furthermore, we highlight the putative variations that diverge from a common ground in an atemporal course that proposes three phases for all relevant molecular events.

Optogenetic and Chemogenic Control of Pain Signaling: Molecular Markers.

Pain is a complex experience that involves physical, emotional, and cognitive aspects. This review focuses specifically on the physiological processes underlying pain perception, with a particular emphasis on the various types of sensory neurons involved in transmitting pain signals to the central nervous system. Recent advances in techniques like optogenetics and chemogenetics have allowed researchers to selectively activate or inactivate specific neuronal circuits, offering a promising avenue for developing more effective pain management strategies. The article delves into the molecular targets of different types of sensory fibers such as channels, for example, TRPV1 in C-peptidergic fiber, TRPA1 in C-non-peptidergic receptors expressed differentially as MOR and DOR, and transcription factors, and their colocalization with the vesicular transporter of glutamate, which enable researchers to identify specific subtypes of neurons within the pain pathway and allows for selective transfection and expression of opsins to modulate their activity.

Body Composition and Risk of Vascular-Metabolic Mortality Risk in 113 000 Mexican Men and Women Without Prior Chronic Disease.

Background Body-mass index is the sum of fat mass index (FMI) and lean mass index (LMI), which vary by age, sex, and impact on disease outcomes. We investigated the separate and joint relevance of FMI and LMI with vascular-metabolic causes of death in Mexican adults. Methods and Results A total of 113 025 adults aged 35 to 74 years and free from diabetes or other chronic diseases when recruited into the Mexico City Prospective Study were followed for 19 years. Cox models estimated sex-specific death rate ratios from vascular-metabolic causes after adjustment for confounders and exclusion of the first 5 years of follow-up. To account for the strong correlation between FMI and LMI, additional models estimated rate ratios associated with "residual FMI" and "residual LMI" (ie, the residuals from linear regression analyses of FMI on LMI, or vice versa). In both sexes, higher FMI and LMI were associated with higher risks of vascular-metabolic mortality. For a given (ie, fixed) level of LMI, the rate ratio (95% CI) for vascular-metabolic mortality per 1 kg/m2 higher residual FMI strengthened and was higher in women (1.52 [1.38-1.68]) than in men (1.19 [1.13-1.25]). By contrast, for a given level of FMI, higher residual LMI was inversely associated with vascular-metabolic mortality (rate ratio per 1 kg/m2 0.67 [0.56-0.80] in women and 0.94 [0.90-0.98] in men). Conclusions In this study, higher residual FMI was more strongly associated with vascular-metabolic mortality in women than in men. Conversely, higher residual LMI was inversely associated with vascular-metabolic mortality, particularly in women.

Predictors of Mechanical Ventilation in Guillain-Barré Syndrome with Axonal Subtypes.

BACKGROUND: The early clinical predictors of respiratory failure in Latin Americans with Guillain-Barré syndrome (GBS) have scarcely been studied. This is of particular importance since Latin America has a high frequency of axonal GBS variants that may imply a worse prognosis. METHODS: We studied 86 Mexican patients with GBS admitted to the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, a referral center of Mexico City, to describe predictors of invasive mechanical ventilation (IMV). RESULTS: The median age was 40 years (interquartile range: 26-53.5), with 60.5% men (male-to-female ratio: 1.53). Most patients (65%) had an infectious antecedent (40.6% gastrointestinal). At admission, 38% of patients had a Medical Research Council (MRC) sum score <30. Axonal subtypes predominated (60.5%), with acute motor axonal neuropathy being the most prevalent (34.9%), followed by acute inflammatory demyelinating polyneuropathy (32.6%), acute motor sensory axonal neuropathy (AMSAN) (25.6%), and Fisher syndrome (7%). Notably, 15.1% had onset in upper limbs, 75.6% dysautonomia, and 73.3% pain. In all, 86% received either IVIg (9.3%) or plasma exchange (74.4%). IMV was required in 39.5% patients (72.7% in AMSAN). A multivariate model without including published prognostic scores yielded the time since onset to admission <15 days, axonal variants, MRC sum score <30, and bulbar weakness as independent predictors of IMV. The model including grading scales yielded lower limbs onset, Erasmus GBS respiratory insufficiency score (EGRIS) >4, and dysautonomia as predictors. CONCLUSION: These results suggest that EGRIS is a good prognosticator of IMV in GBS patients with a predominance of axonal electrophysiological subtypes, but other early clinical data should also be considered.

Osmotic demyelination syndrome in patients with non-Hodgkin lymphoma: a case report and literature review.

INTRODUCTION: Osmotic demyelination syndrome (ODS) is a non-inflammatory process of the central nervous system caused by extracellular osmotic changes, which leads to oligodendrocyte apoptosis and disruption of myelin sheaths, usually affecting patients with underlying systemic conditions that impose susceptibility to osmotic stress. Description of ODS in patients with non-Hodgkin lymphoma (NHL) is limited to a few case reports. METHODS: Here, we report a 44-year-old man with NHL that had an incidental diagnosis of ODS. We conducted a literature review of the published cases of ODS in NHL patients from 1959 to 2020, aiming to describe the characteristics of these patients. RESULTS: A total of seven patients were summarized (four men and three women), including our case and six patients from published reports. Risk factors such as weight loss and alcoholism were reported in five (71.4%) patients. Hyponatremia was found in six (85.7%) of the cases, and none of them had overly rapid sodium correction. Four cases were asymptomatic, and diffuse large B-cell lymphoma was the most common subtype of NHL (85.7%). The outcome was favorable in most cases; only two deaths not directly related to ODS were reported. CONCLUSION: We wish to suggest that systemic and metabolic stress induced by NHL may be associated with the development of central osmotic demyelination, and therefore, NHL may be a novel risk factor for ODS. Clinicians should be aware of ODS in patients with hematological malignancies, even in the absence of traditional risk factors.

Psychological and Psychiatric Events Following Immunization with Five Different Vaccines against SARS-CoV-2.

BACKGROUND: Despite the high number of vaccines administered against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, the information on the psychological/psychiatric adverse events following immunization (AEFI) with these newly developed vaccines remains scarce. OBJECTIVE: To describe the frequency of psychological/psychiatric symptoms among recipients of five different anti-SARS-CoV-2 vaccines and to explore the factors associated with their development reported in the nationwide Mexican registry of AEFI against SARS-CoV-2. METHODS: Descriptive study of all the psychological/psychiatric symptoms, including anxiety, panic attacks, insomnia, and agitation reported to the Mexican Epidemiological Surveillance System from 21 December 2020 to 27 April 2021, among adult (≥18 years old) recipients of 7,812,845 doses of BNT162b2, ChAdOx1 nCov-19, rAd26-rAd5, Ad5-nCoV, or CoronaVac. The factors associated with their development are determined by multivariate regression analysis. RESULTS: There were 19,163 AEFI reports during the study period; amongst them, 191 (1%) patients had psychological/psychiatric symptoms (median age of 41 years, interquartile range of 32-54; 149 [78%] women) for an observed incidence of 2.44 cases per 100,000 administered doses (95% confidence interval [CI] 2.12-2.82), 72.8% of psychiatric AEFIs were reported among recipients of BNT162b2. The median time from vaccination to symptom onset was 35 min (interquartile range: 10-720). Overall, the most common psychological/psychiatric symptoms were anxiety in 129 (67.5%) patients, panic attacks in 30 (15.7%), insomnia in 25 (13%), and agitation in 11 (5.7%). After adjusting for the confounding factors, the odds for developing psychological/psychiatric symptoms were higher for those concurrently reporting syncope (odds ratio [OR]: 4.73, 95% CI: 1.68-13.33); palpitations (OR: 2.47, 95% CI: 1.65-3.70), and dizziness (OR: 1.59, 95% CI: 1.10-2.28). CONCLUSION: In our population, psychological/psychiatric symptoms were extremely infrequent AEFIs. No severe psychiatric AEFIs were reported. Immunization stress-related responses might explain most of the detected cases.

Humoral response to different SARS-CoV-2 vaccines in orthotopic liver transplant recipients.

BACKGROUND: The safety and efficacy data of the different types of available vaccines is still needed. The goal of the present analysis was to evaluate the humoral response to the COVID-19 vaccines in orthotopic liver transplant (OLT) recipients. METHODS: Participants were included from February to September 2021. No prioritized vaccination roll call applied for OLT patients. Controls were otherwise healthy people. Blood samples were drawn after 15 days of the complete vaccine doses. The samples were analyzed according to the manufacturer's instructions using the Liaison XL platform from DiaSorin (DiaSorin S.p.A., Italy), and SARS-COV-2 IgG II Quant (Abbott Diagnostics, IL, USA). RESULTS: A total of 187 participants (133 OLT, 54 controls, median age: 60 years, 58.8% women) were included for the analysis; 74.3% had at least one comorbidity. The serologic response in OLT patients was lower than in controls (median 549 AU/mL vs. 3450 AU/mL, respectively; p = 0.001). A positive humoral response was found in 133 OLT individuals: 89.2% with BNT162b2 (Pfizer-BioNTech), 60% ChAdOx1 nCOV-19 (Oxford-AstraZeneca), 76.9% with CoronaVac (Sinovac, Life Sciences, China), 55.6% Ad5-nCov (Cansino, Biologics), 68.2% Gam-COVID-Vac (Sputnik V) and 100% with mRNA-1273. In controls the serological response was 100%, except for Cansino (75%). In a multivariable model, personal history of COVID-19 and BNT162b2 inoculation were associated with the serologic response, while the use of prednisone (vs. other immunosuppressants) reduced this response. CONCLUSION: The serologic response to COVID-19 vaccines in OLT patients is lower than in healthy controls. The BNT162b2 vaccine was associated with a higher serologic response.

Acute Stroke Care in Mexico City: The Hospital Phase of a Stroke Surveillance Study.

Background: Acute stroke care has greatly improved in recent decades. However, the increasing stroke mortality in low-to-middle income countries suggests that progress has not been reached completely by these populations. Here we present the analysis of the hospital phase of the first population-based stroke surveillance study. Methods: A daily hospital surveillance method was used to identify adult patients with acute stroke during 18 months in six hospitals. We abstracted data on demographics, vascular risk factors, neuroimaging-confirmed stroke types, and clinical data. Results: A total of 1361 adults with acute stroke were identified (mean age 69.2 years; 52% women) with transient ischemic attack (5.5%), acute ischemic stroke (68.6%), intracerebral hemorrhage (23.1%), cerebral venous thrombosis (0.2%), and undetermined stroke (2.6%). The main risk factors were hypertension (80.7%) and diabetes mellitus (47.6%). The usage rate of thrombolysis was 3.6%, in spite of the fact that 37.2% of acute ischemic stroke patients arrived in <4.5 h. The 30-day case fatality rate was 32.6%, higher in hemorrhagic than ischemic stroke. Conclusion: We identified limitations in acute stroke care in the Mexico City, including neuroimaging availability and thrombolysis usage. The door-to-door phase will help to depict the acute stroke burden in Mexico.

Incidence of Guillain-Barré syndrome following SARS-CoV-2 immunization: Analysis of a nationwide registry of recipients of 81 million doses of seven vaccines.

BACKGROUND AND PURPOSE: Information on Guillain-Barré syndrome (GBS) as an adverse event following immunization (AEFI) against SARS-CoV-2 remains scarce. We aimed to report GBS incidence as an AEFI among adult (≥18 years) recipients of 81,842,426 doses of seven anti-SARS-CoV-2 vaccines between December 24, 2020, and October 29, 2021, in Mexico. METHODS: Cases were retrospectively collected through passive epidemiological surveillance. The overall observed incidence was calculated according to the total number of administered doses. Vaccines were analyzed individually and by vector as mRNA-based (mRNA-1273 and BNT162b2), adenovirus-vectored (ChAdOx1 nCov-19, rAd26-rAd5, Ad5-nCoV, and Ad26.COV2-S), and inactivated whole-virion-vectored (CoronaVac) vaccines. RESULTS: We identified 97 patients (52 males [53.6%]; median [interquartile range] age 44 [33-60] years), for an overall observed incidence of 1.19/1,000,000 doses (95% confidence interval [CI] 0.97-1.45), with incidence higher among Ad26.COV2-S (3.86/1,000,000 doses, 95% CI 1.50-9.93) and BNT162b2 recipients (1.92/1,00,000 doses, 95% CI 1.36-2.71). The interval (interquartile range) from vaccination to GBS symptom onset was 10 (3-17) days. Preceding diarrhea was reported in 21 patients (21.6%) and mild COVID-19 in four more (4.1%). Only 18 patients were tested for Campylobacter jejuni (positive in 16 [88.9%]). Electrophysiological examinations were performed in 76 patients (78.4%; axonal in 46 [60.5%] and demyelinating in 25 [32.8%]); variants were similar across the platforms. On admission, 91.8% had a GBS disability score ≥3. Seventy-five patients (77.3%) received intravenous immunoglobulin, received seven plasma exchange (7.2%), and 15 (15.5%) were treated conservatively. Ten patients (10.3%) died, and 79.1% of survivors were unable to walk independently. CONCLUSIONS: Guillain-Barré syndrome was an extremely infrequent AEFI against SARS-CoV-2. The protection provided by these vaccines outweighs the risk of developing GBS.

Headache related to personal protective equipment in healthcare workers during COVID-19 pandemic in Mexico: baseline and 6-month follow-up.

BACKGROUND AND AIM: Headaches related to the use of personal protective equipment (PPE) could affect performance at work in healthcare personnel. Our aim was to describe the prevalence and risk factors for headaches related to PPE, in the personnel of a specialized coronavirus disease 2019 (COVID-19) tertiary hospital. METHODS: In this cross-sectional survey study, we invited healthcare workers from COVID-19 referral center in Mexico (May 22-June 19, 2020) to answer a standardized structure questionnaire on characteristics of new-onset PPE-related headache or exacerbation of primary headache disorder. Participants were invited regardless of whether they had a current headache to avoid selection bias. This is the primary analysis of these data. RESULTS: Two hundred and sixty-eight subjects were analyzed, 181/268 (67.5%) women, 177/268 (66%) nurses, mean age 28 years. The prevalence of PPE-related headache was 210/268 (78.4%). Independent risk factors were occupation other than physician (OR 1.59, 95% CI 1.20-2.10), age > 30 years (OR 2.54, 95% CI 1.25-5.14), and female sex (OR 3.58, 95% CI 1.86-6.87). In the 6-month follow-up, 13.1% of subjects evolve to chronic headache, with stress as predictive risk factor. CONCLUSION: The frequency of PPE-associated headache is high, and a subgroup could evolve to chronic headache. More studies are necessary to improve the knowledge about this condition.

Ethnicity and other COVID-19 death risk factors in Mexico.

Introduction: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop coronavirus disease 2019 (COVID-19). Risk factors associated with death vary among countries with different ethnic backgrounds. We aimed to describe the factors associated with death in Mexicans with confirmed COVID-19. Material and methods: We analysed the Mexican Ministry of Health's official database on people tested for SARS-CoV-2 infection by real-time reverse transcriptase-polymerase chain reaction (rtRT-PCR) of nasopharyngeal fluids. Bivariate analyses were performed to select characteristics potentially associated with death, to integrate a Cox-proportional hazards model. Results: As of May 18, 2020, a total of 177,133 persons (90,586 men and 86,551 women) in Mexico received rtRT-PCR testing for SARS-CoV-2. There were 5332 deaths among the 51,633 rtRT-PCR-confirmed cases (10.33%, 95% CI: 10.07-10.59%). The median time (interquartile range, IQR) from symptoms onset to death was 9 days (5-13 days), and from hospital admission to death 4 days (2-8 days). The analysis by age groups revealed that the significant risk of death started gradually at the age of 40 years. Independent death risk factors were obesity, hypertension, male sex, indigenous ethnicity, diabetes, chronic kidney disease, immunosuppression, chronic obstructive pulmonary disease, age > 40 years, and the need for invasive mechanical ventilation (IMV). Only 1959 (3.8%) cases received IMV, of whom 1893 were admitted to the intensive care unit (96.6% of those who received IMV). Conclusions: In Mexico, highly prevalent chronic diseases are risk factors for death among persons with COVID-19. Indigenous ethnicity is a poorly studied factor that needs more investigation.

Influence of Weight Loss on Cognitive Functions: A Pilot Study of a Multidisciplinary Intervention Program for Obesity Treatment.

There is a relationship between obesity and cognitive functioning. Our aim was to assess weight loss influence on global cognition and executive functioning (EF) in adults with obesity under a multidisciplinary weight loss program. In this six-month longitudinal study, we assessed 81 adults (age < 50 years) with body mass index (BMI) ≥ 30. EF and global cognitive performance were evaluated with the Montreal Cognitive Assessment (MoCA), Neuropsychological Battery of Executive Functions (BANFE-2) and Trail Making Test-Part B (TMT-B). Median age was 40.0 years (IQR: 31.5−47, 61% women), and the median BMI was 41.4 (IQR: 36.7−45.9). At a six-month follow-up, the mean weight loss was 2.67% (29.6% of patients achieved ≥5% weight loss). There was an improvement in EF evaluated with BANFE (p = 0.0024) and global cognition with MoCA (p = 0.0024). Women experienced more remarkable change, especially in EF. Weight loss did not correlate with cognitive performance, except for TMT-B (r-0.258, p = 0.026). In the regression analysis, only years of education predicted the MoCA score. This study showed that patients improved cognitive performance during the follow-up; nevertheless, the magnitude of weight loss did not correlate with cognitive improvement. Future studies are warranted to demonstrate if patients achieving ≥5% weight loss can improve cognition, secondary to weight loss.

Antiphospholipid syndrome-mediated acute cerebrovascular diseases and long-term outcomes.

OBJECTIVES: The antiphospholipid syndrome (APS) is an autoimmune disease associated with thrombotic and non-thrombotic neurologic manifestations. APS is classified as primary (PAPS) or secondary (SAPS) when it co-exists with another autoimmune disease. We aim to describe the spectrum of acute cerebrovascular disease among patients with APS, their differences between stroke subtypes, and long-term functional outcomes. METHODS: Retrospective cohort study including adult (≥18 years) patients with APS followed in the stroke clinic of a tertiary-care reference center for autoimmune diseases in Mexico from 2009 to 2019. RESULTS: We studied 120 cases; 99 (82.5%) women; median age 43 years (interquartile range 35-52); 63.3% with SAPS. Demographics, comorbidities, and antiphospholipid antibodies (aPL) positivity were similar between APS type and stroke subtypes. Amongst index events, we observed 84 (70%) acute ischemic strokes (AIS), 19 (15.8%) cerebral venous thromboses (CVT), 11 (9.2%) intracerebral hemorrhages (ICH), and six (5%) subarachnoid hemorrhages (SAH). Sixty-seven (55.8%) were known patients with APS; the median time from APS diagnosis to index stroke was 46 months (interquartile range 12-96); 64.7% of intracranial hemorrhages (ICH or SAH) occurred ≥4 years after APS was diagnosed (23.5% anticoagulation-related); 63.2% of CVT cases developed before APS was diagnosed or simultaneously. Recurrences occurred in 26 (22.8%) patients, AIS, in 18 (69.2%); intracranial hemorrhage, in eight (30.8%). Long-term functional outcomes were good (modified Rankin Scale ≤2) in 63.2% of cases, during follow-up, the all-cause mortality rate was 19.2%. CONCLUSION: We found no differences between stroke subtypes and APS types. aPL profiles were not associated with any of the acute cerebrovascular diseases described in this cohort. CVT may be an initial thrombotic manifestation of APS with low mortality and good long-term functional outcome.

Critical role of acute hypoxemia on the cognitive impairment after severe COVID-19 pneumonia: a multivariate causality model analysis.

BACKGROUND: A high proportion of coronavirus disease 2019 (COVID-19) survivors may develop long-term cognitive impairment. We aimed to develop a multivariate causal model exposing the links between COVID-19-associated biomarkers, illness-related variables, and their effects on cognitive performance. METHODS: In this prospective study, we assess the potential drivers for the development of cognitive impairment in patients with severe COVID-19 pneumonia aged ≥ 18 years at 6-month follow-up after hospital discharge, using the Montreal Cognitive Assessment (MoCA). Patients with pre-existing cognitive impairment were excluded. Laboratory results at hospital admission were clustered by principal component analysis (PCA) and included in a path analysis model evaluating the causal relationship between age, comorbidities, hypoxemia, invasive mechanical ventilation (IMV) requirement, in-hospital delirium, and cognitive performance. RESULTS: We studied 92 patients: 54 (58.7%) men and 38 (41.3%) women, with median age of 50 years (interquartile range 42-55), among whom 50 (54.4%) tested positive for cognitive impairment at 6-month follow-up. Path analysis revealed a direct link between the thrombo-inflammatory component of PCA (C-reactive protein, fibrinogen, and neutrophils) and hypoxemia severity at hospital admission. Our model showed that low PaO2/FiO2 ratio values, unlike the thrombo-inflammatory component, had a direct effect on cognitive performance, independent from age, in-hospital delirium, and invasive mechanical ventilation. CONCLUSION: In this study, biomarkers of thrombo-inflammation in COVID-19 and low PaO2/FiO2 had a negative effect on cognitive performance 6 months after hospital discharge. These results highlight the critical role of hypoxemia as a driver for impaired cognition in the mid-term.

Delirium and Associated Factors in a Cohort of Hospitalized Patients With Coronavirus Disease 2019.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic dramatically increased the number of patients requiring treatment in an intensive care unit or invasive mechanical ventilation worldwide. Delirium is a well-known neuropsychiatric complication of patients with acute respiratory diseases, representing the most frequent clinical expression of acute brain dysfunction in critically ill patients, especially in those undergoing invasive mechanical ventilation. Among hospitalized patients with COVID-19, delirium incidence ranges from 11% to 80%, depending on the studied population and hospital setting. OBJECTIVE: To determine risk factors for the development of delirium in hospitalized patients with COVID-19 pneumonia. METHODS: We retrospectively studied consecutive hospitalized adult (≥18 y) patients with confirmed COVID-19 pneumonia from March 15 to July 15, 2020, in a tertiary-care hospital in Mexico City. Delirium was assessed by the attending physician or trained nurse, with either the Confusion Assessment Method for the Intensive Care Unit or the Confusion Assessment Method brief version, according to the appropriate diagnostic tool for each hospital setting. Consultation-liaison psychiatrists and neurologists confirmed all diagnoses. We calculated adjusted hazard ratios (aHR) with 95% confidence interval (CI) using a Cox proportional-hazards regression model. RESULTS: We studied 1017 (64.2% men; median age, 54 y; interquartile range 44-64), of whom 166 (16.3%) developed delirium (hyperactive in 75.3%); 78.9% of our delirium cases were detected in patients under invasive mechanical ventilation. The median of days from admission to diagnosis was 14 (interquartile range 8-21) days. Unadjusted mortality rates between delirium and no delirium groups were similar (23.3% vs. 24.1; risk ratio 0.962, 95% CI 0.70-1.33). Age (aHR 1.02, 95% CI 1.01-1.04; P = 0.006), an initial neutrophil-to-lymphocyte ratio ≥9 (aHR 1.81, 95% CI 1.23-2.65; P = 0.003), and requirement of invasive mechanical ventilation (aHR 3.39, 95% CI 1.47-7.84; P = 0.004) were independent risk factors for in-hospital delirium development. CONCLUSIONS: Delirium is a common in-hospital complication of patients with COVID-19 pneumonia, associated with disease severity; given the extensive number of active COVID-19 cases worldwide, it is essential to detect patients who are most likely to develop delirium during hospitalization. Improving its preventive measures may reduce the risk of the long-term cognitive and functional sequelae associated with this neuropsychiatric complication.