The hemostatic system in chronic brain diseases: A new challenging frontier?

Neurological diseases (ND), including neurodegenerative diseases (NDD) and psychiatric disorders (PD), present a significant public health challenge, ranking third in Europe for disability and premature death, following cardiovascular diseases and cancers. In 2017, approximately 540 million cases of ND were reported among Europe's 925 million people, with strokes, dementia, and headaches being most prevalent. Nowadays, more and more evidence highlight the hemostasis critical role in cerebral homeostasis and vascular events. Indeed, hemostasis, thrombosis, and brain abnormalities contributing to ND form a complex and poorly understood equilibrium. Alterations in vascular biology, particularly involving the blood-brain barrier, are implicated in ND, especially dementia, and PD. While the roles of key coagulation players such as thrombin and fibrinogen are established, the roles of other hemostasis components are less clear. Moreover, the involvement of these elements in psychiatric disease pathogenesis is virtually unstudied, except in specific pathological models such as antiphospholipid syndrome. Advanced imaging techniques, primarily functional magnetic resonance imaging and its derivatives like diffusion tensor imaging, have been developed to study brain areas affected by ND and to improve our understanding of the pathophysiology of these diseases. This literature review aims to clarify the current understanding of the connections between hemostasis, thrombosis, and neurological diseases, as well as explore potential future diagnostic and therapeutic strategies.

Use of neurofilament light chain to identify structural brain diseases in dogs.

BACKGROUND: Neurofilament light chain (NfL) is released into the peripheral circulation by damaged axons. OBJECTIVES: To evaluate the diagnostic value of serum NfL concentration in dogs with intracranial diseases. ANIMALS: Study included 37 healthy dogs, 31 dogs with idiopathic epilepsy (IE), 45 dogs with meningoencephalitis of unknown etiology (MUE), 20 dogs with hydrocephalus, and 19 dogs with brain tumors. METHODS: Cohort study. Serum NfL concentrations were measured in all dogs using single-molecule array technology. RESULTS: Serum NfL concentration in dogs with each structural disease was significantly higher than in healthy dogs and dogs with IE (P = .01). The area under the receiver operating characteristic curve of NfL for differentiating between dogs with structural diseases and IE was 0.868. An optimal cutoff value of the NfL 27.10 pg/mL had a sensitivity of 86.67% and a specificity of 74.19% to differentiate the dogs with IE from those with structural brain diseases. There were significant correlations between NfL concentrations and lesion size: (1) MUE, P = .01, r = 0.429; (2) hydrocephalus, P = .01, r = 0.563. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum NfL could be a useful biomarker for distinguishing IE from structural diseases in dogs and predicting the lesion sizes of MUE and hydrocephalus.

Prognostic value of systemic immune-inflammation index and monocyte-to-HDL-cholesterol ratio in early cardio-cerebral complications in elderly patients with acute severe carbon monoxide poisoning.

To investigate how effectively systemic immune-inflammation index (SII) and Monocyte-to-HDL-cholesterol ratio (MHR) predict the development of early cardio-cerebral complications in elderly patients who have experienced acute severe carbon monoxide poisoning (ASCMP). A retrospective analysis was conducted on 77 elderly patients with ASCMP admitted to the emergency department of Harrison International Peace Hospital from November 2020 to March 2022. The prevalence of early-onset complications among the 77 individuals was 38.96%. Binary Logistics regression analysis showed that SII and MHR were independent influencing factors of early cardio-cerebral complications in elderly patients with ASCMP. The complication group had a longer length of stay, a greater mortality rate, and a higher incidence of delayed encephalopathy after acute carbon monoxide poisoning (p < .05) than the non-complication group. The area under the curve (AUC) of SII and MHR in predicting early cardio-cerebral complications in elderly patients with ASCMP were 0.724 and 0.796, respectively, with 80.0% and 63.3% sensitivity, and 61.7% and 87.2% specificity. The incidence of early cardio-cerebral complications in elderly patients who had ASCMP is high and the prognosis is poor. SII and MHR can be utilized as independent predictors of early cardio-cerebral complications in elderly patients with ASCMP, allowing doctors to diagnose and treat cardio-cerebral complications earlier and improve prognosis.

NRBC concentrations over time in neonates with moderate to severe neonatal encephalopathy with and without sentinel events.

OBJECTIVE: To study the serum concentrations of nucleated red blood cells (NRBC) over time in neonates with moderate to severe neonatal encephalopathy (NE). STUDY DESIGN: A retrospective cohort study with subjects subdivided into three groups: definite sentinel events (n = 52), probable sentinel events (n = 20) and no history of sentinel events (n = 63). Peak absolute NRBC and NRBC/100 WBC were compared between groups and with MRI Injury score, cord and admission pH/base deficit. RESULTS: Absolute NRBC peaked at 24.05 h after birth (CI: 15.30-32.79), 17.56 h after birth (CI: 7.35-27.77), and 39.81 h after birth (CI: 28.73-50.89) in each respective group. The peak in absolute NRBC correlated with the severity of injury in the grey matter in group 2 and white matter in groups 1 and 2. Higher peak absolute NRBC value correlated to a lower admission ABG pH. CONCLUSION: NRBC peak at 24 h after birth in neonates with sentinel events.

Central Retinal Artery Occlusion in Rhino-Orbital-Cerebral Mucormycosis: An Inflammatory-Prothrombotic State.

PURPOSE: The aim was to evaluate patient profiles of rhino-orbital-cerebral mucormycosis (ROCM) cases with central retinal artery occlusion (CRAO) postcoronavirus disease 2019. DESIGN: A nonrandomized retrospective case-control study. METHODS: The ROCM cases presenting with CRAO were compared with a control ROCM group without CRAO at a tertiary care center. Demography, systemic status, clinical features, histopathology, imaging, and blood profile were assessed for any specific risk factors. RESULTS: A total of 12 patients were seen in the CRAO group and 16 in the non-CRAO group. The male-to-female ratio was 3:1 with a mean age of 49.5 years. In the CRAO group, 75% had diabetes mellitus with mean hemoglobin A1c of 9.03%, and 66.7% had received steroid treatment. All cases were histopathologically confirmed positive for mucor. There was a significant difference in mean D-dimer and serum ferritin between the 2 groups, with higher level in the CRAO group. All patients with CRAO had light perception-negative vision, with total ophthalmoplegia and proptosis seen in 66.7% of cases. Four patients had orbital apex involvement, 5 had cavernous sinus involvement, and 8 had intracranial involvement in the CRAO group. CONCLUSIONS: Inflammatory markers D-dimer and serum ferritin were significantly associated with CRAO, suggestive of hyperinflammatory and hypercoagulable state. A high index of suspicion should be maintained in cases with elevated markers and prophylactic anticoagulants can be started to prevent CRAO in a subset of patients.

Altered distributions and functions of natural killer T cells and γδ T cells in neonates with neonatal encephalopathy, in school-age children at follow-up, and in children with cerebral palsy.

We enumerated conventional and innate lymphocyte populations in neonates with neonatal encephalopathy (NE), school-age children post-NE, children with cerebral palsy and age-matched controls. Using flow cytometry, we demonstrate alterations in circulating T, B and natural killer cell numbers. Invariant natural killer T cell and Vδ2+ γδ T cell numbers and frequencies were strikingly higher in neonates with NE, children post-NE and children with cerebral palsy compared to age-matched controls, whereas mucosal-associated invariant T cells and Vδ1 T cells were depleted from children with cerebral palsy. Upon stimulation ex vivo, T cells, natural killer cells and Vδ2 T cells from neonates with NE more readily produced inflammatory cytokines than their counterparts from healthy neonates, suggesting that they were previously primed or activated. Thus, innate and conventional lymphocytes are numerically and functionally altered in neonates with NE and these changes may persist into school-age.

Parameters Indicating Development of Influenza-Associated Acute Necrotizing Encephalopathy: Experiences from a Single Center.

BACKGROUND Influenza-associated acute necrotizing encephalopathy (IANE) can be lethal and disabling and have a sudden onset and deteriorate rapidly but lacks early diagnostic indicators. We aimed to examine the early clinical diagnostic indicators in children with IANE. MATERIAL AND METHODS Acute influenza patients were grouped according to their clinical manifestations: flu alone (FA), flu with febrile seizure (FS), influenza-associated encephalopathy (IAE), and IANE. The clinical features, biomarkers, neuroelectrophysiological results, and neuroimaging examination results were compared. RESULTS A total of 31 patients were included (FA (n=4), FS (n=8), IAE (n=14), and IANE (n=5)). The IANE group, whose mean age was 3.7 years, was more likely to show rapid-onset seizure, acute disturbance of consciousness (ADOC), Babinski's sign, and death/sequela. More patients in the IANE group required tracheal intubation mechanical ventilation and received intravenous immunoglobulins (IVIG) and glucocorticoids. The alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels in the IANE group were significantly higher than in the FS and IAE groups. The aquaporin-4 (AQP-4) antibody and malondialdehyde (MDA) levels in the serum and cerebrospinal fluid (CSF) were notably higher in IANE patients in the acute stage compared with FS and IAE patients. All patients in the IANE group had positive neuroimaging findings. CONCLUSIONS Early clinical warning factors for IANE include rapid-onset seizures in patients under 4 years of age, ADOC, and pathological signs. Increased AQP-4 antibodies and MDA levels in CSF might contribute to early diagnosis. Early magnetic resonance venography (MRV) and susceptibility-weighted imaging (SWI) sequences, or thrombelastography to identify deep vein thrombosis, might indicate clinical deterioration.

Successful mild brain hypothermia therapy followed by targeted temperature management for pediatric hemorrhagic shock and encephalopathy syndrome.

OBJECTIVE: Hemorrhagic shock and encephalopathy syndrome (HSES) is the most severe form of acute encephalopathy that progresses rapidly, often resulting in death or severe neurological sequelae. We report the case of a 4-year-old girl with HSES with shock and impaired consciousness. PATIENT AND METHODS: Blood test results showed hypercytokinemia, and the 4-year-old patient was immediately admitted to the intensive care unit. Within 4 h of symptom onset, she received mild brain hypothermia therapy with a target body temperature of 35°C. Methylprednisolone pulse, high dose immunoglobulin, and large doses of circulatory drugs were administered. RESULTS: After 72 h of brain hypothermia therapy, targeted temperature management with a target body temperature between 36°C and 37°C was continued for 96 h. The patient was diagnosed with HSES based on acute encephalopathy with shock, hypercytokinemia, low platelet count, coagulation disorder, renal damage, and intestinal bleeding. Magnetic resonance imaging results revealed no signs of any specific acute encephalopathy. She was discharged without neurological sequelae 28 days after symptom onset. CONCLUSIONS: Mild brain hypothermia therapy initiated in the early stages followed by targeted temperature management may be an effective way to improve neurological outcomes in children suffering from HSES.

MiRNA-124a: a Potential Biomarker for Neurological Deficits Following Cardiac Surgery in Pediatric Patients.

Brain injury is a major source of patient morbidity after cardiac surgery in children. New early accurate biomarkers are needed for the diagnosis of patients at risk for cerebral postoperative damage. Specific circulating miRNAs have been found as suitable biomarkers for many diseases. We tested whether miRNA-124a reflects neurological injury in pediatric patients following heart surgery. Serum samples were obtained from 34 patients before and six hours after heart surgery. MiRNAs-124a was quantified by RQ-PCR. MiRNA-124a levels six hours after heart surgery correlated with the neurological outcome of the patients. In children with neurological deficits, miRNA-124a levels increased while in those with no neurological deficits the levels decreased. MiRNA-124a was able, at six hours after the operation, to identify patients who are at risk for the appearance of neurological deficits. Circulating miRNA-124a is a potential biomarker for the appearance of neurological deficits in pediatric patients following heart surgery. Graphical Abstract.

Hematological findings associated with tubulin-folding cofactors D-related encephalopathy: Expanding the phenotype.

The dysfunction of microtubules (α/ß-tubulin polymers) underlies a wide range of nervous system genetic abnormalities. Defects in TBCD, a tubulin-folding cofactor, cause diseases highlighted with early-onset encephalopathy with or without neurodegeneration, intellectual disability, seizures, microcephaly and tetraparaperesis. Utilizing various molecular methods, we describe nine patients from four unrelated families with two novel exon 18 variants in TBCD exhibiting the typical neurological phenotype of the disease. Interestingly, all the investigated patients had previously unreported hematological findings in the form of neutropenia and mild degree of anemia and thrombocytopenia. In addition to delineating the neurological phenotype in several patients with TBCD variants, our study stresses on the new association of neutropenia, in particular, with the disease.

Elevated cytokine, chemokine, and growth and differentiation factor-15 levels in hemorrhagic shock and encephalopathy syndrome: A retrospective observational study.

Patients with hemorrhagic shock and encephalopathy syndrome (HSES) have a high early mortality rate, which may be caused by a 'cytokine storm'. However, there is little information on how cytokines and chemokines change over time in these patients. We aimed to describe the characteristics of HSES by examining changes in serum biomarker levels over time. Six patients with HSES were included. We retrospectively evaluated their clinical course and imaging/laboratory data. We measured serum levels of multiple cytokines [interleukin 1ß (IL-1ß), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-gamma, and tumor necrosis factor alpha], chemokines (IL-8, monocyte chemoattractant protein-1, interferon-inducible protein-10), and growth and differentiation factor (GDF)-15. The highest cytokine and chemokine levels were noted in the first 24 h, and decreased thereafter. The GDF-15 level was markedly high. Cytokine, chemokine, and GDF-15 levels were significantly higher in patients with HSES than in controls in the first 24 h, except for IL-2 and IL-4. Patients with HSES have high inflammatory cytokine and chemokine levels, a high GDF-15 level in the first 24 h, and high lactate levels. Our study provides new insights on the pathophysiology of HSES, a detailed clinical picture of patients with HSES, and potential biomarkers.

Clinical analysis of reversible splenial lesion syndrome in Chinese adults: A retrospective study of 11 cases.

Reversible splenial lesion syndrome (RESLES) is a clinico-radiological entity that defines a reversible lesion in the splenium of the corpus callosum (SCC) on magnetic resonance imaging (MRI). The clinical and radiological characteristics of RESLES are poorly defined and most RESLES literature is in the form of case reports. We reviewed the clinical and radiological data from 11 RESLES patients in order to more clearly describe the characteristics of this disorder in adults.Patients included in this study were diagnosed with RESLES from May 2012 to March 2018. We collected clinical, imaging, and laboratory data of 11 adult patients from Neurology Department of the Affliated Yantai Yuhuangding Hospital of Qingdao University. After analyzing various clinico-radiological features and laboratory parameters, including serum sodium, pathogen testing, cerebrospinal fluid (CSF) studies, electroencephalography (EEG), and MRI findings, we made a diagnosis of RESLES based on the criteria proposed previously by Garcia-Monco et al.Of the 11 patients, 7 (63.63%) were male and 4 (36.36%) were female, ranging in age from 24 to 62 years with an average age of 31.48 ±â€Š11.47 years. Seven cases occurred in the months of winter and spring (December-March). The primary clinical symptoms were headache, seizure, disturbance of consciousness, mental abnormality, and dizziness. All 11 patients had lesions in the SCC and all the lesions disappeared or significantly improved on follow-up imaging that was done within a month of symptom resolution.We found 5 (45.45%) patients had a CSF opening pressure >180 mmH2O, in addition to elevated protein and(or) leukocytes levels in 3 (27.27%) patients. The serum sodium concentration in 6 (54.55%) patients was low (<137 mmol/L) and EEG showed nonspecific slowing in waves 4 (36.36%) patients.When we encounter clinical manifestations such as headache accompanied with mental symptoms, disturbance of consciousness or epilepsy, and brain MRI finds lesions of the corpus callosum, we should consider whether it is RESLES. In order to find out the possible cause of the disease, we should carefully inquire about the history of the disease, complete etiology examination, and CSF tests. Of course, it is one of the necessary conditions for the diagnosis that the lesions in the corpus callosum are obviously relieved or disappeared.

Evaluating the Low-Dose ACTH Stimulation Test in Neonates: Ideal Times for Cortisol Measurement.

CONTEXT: Low-dose adrenocorticotropic hormone stimulation testing (LDST) can be used to diagnose central adrenal insufficiency. However, uncertainty remains over optimal times to draw serum cortisol levels. OBJECTIVE: To determine optimal times to draw serum cortisol levels for the LDST in neonates. DESIGN: A retrospective chart review of LDSTs performed on neonates from January 1, 2009 to September 30, 2017. SETTING: Children's Hospital of Eastern Ontario (CHEO), a tertiary-care outborn pediatric center. PATIENTS: Forty-nine patients were included: 23 (46.9%) born at term, 12 (24.5%) born very preterm to late preterm, and 14 (28.6%) born extremely preterm. INTERVENTION: Cortisol levels were drawn at baseline and 15, 30, and 60 minutes following administration of Cortrosyn 1 mcg/kg (maximum dose 1 mcg). MAIN OUTCOME MEASURE: Timing of peak cortisol level and marginal value of drawing a second and third cortisol sample at 15, 30, or 60 minutes was determined. RESULTS: Cortisol peaked at 15-, 30-, and 60-minute sampling times for 4%, 27%, and 69% of patients, respectively. The probability that a failed LDST changes to a pass by adding a 15- or 30-minute sample to the superior 60 minute sample is 5.6% (1% to 25.8%) and 11% (3.1% to 32.6%), respectively, for a cortisol pass threshold of 18.1mcg/dL (500 nmol/L). CONCLUSIONS: In contrast to studies of older children, we found that the majority of neonatal LDST cortisol peaks occurred at the 60-minute sampling time with the addition of a 30-minute sample providing substantial benefit. It is questionable if a 15-minute sample provides any benefit, making a case to revise LDST protocols to sample cortisol later for neonates.

[Preliminary analysis of central paroxysmal positional vertigo].

Objective: To explore the possible pathogenesis of central paroxysmal positional vertigo (CPPV) by analyzing its clinical manifestations and characteristics. Methods: The clinical data of 3 patients with CPPV, including 1 male and 2 females, aged 36, 14 and 70 years old respectively, were collected from the Department of Otorhinolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from June 2014 to June 2018. The clinical symptoms, nystagmus, other central ocular motor abnormalities, MRI, PET-CT, and laboratory findings were analyzed retrospectively. Results: All patients showed transient vertigo and nystagmus induced by head changes relative to gravity, but the characteristics of nystagmus did not conform to the typical characteristics of nystagmus in benign paroxysmal positional vertigo. None of patients response to repositioning maneuvers, and all patients presented with the signs of abnormal visual oculomotor system or other symptoms of central system. MRI, PET-CT and blood biochemical tests confirmed that the causes of CPPV in the patients were chronic hemorrhage, inflammation and paraneoplastic cerebellar degeneration. Although the etiology of the three cases is different, the lesion site is involved in the central velocity storage mechanism. Conclusion: The damage of central velocity storage mechanism may lead to the damage of feedback rotation signal correction pathway, and CPPV appears when the head position changes relative to gravity.

Plasma and Cerebrospinal Fluid Candidate Biomarkers of Neonatal Encephalopathy Severity and Neurodevelopmental Outcomes.

OBJECTIVES: To identify candidate biomarkers in both plasma and cerebrospinal fluid (CSF) that are associated with neonatal encephalopathy severity measured by encephalopathy grade, seizures, brain injury by magnetic resonance imaging (MRI), and neurodevelopmental outcomes at 15-30 months. STUDY DESIGN: A retrospective cohort study of plasma (N = 155, day of life 0-1) and CSF (n = 30, day of life 0-7) from neonates with neonatal encephalopathy and healthy neonates born at term (N = 30, ≥36 weeks of gestation) was conducted. We measured central nervous system necrosis (glial fibrillary acidic protein [GFAP], neurogranin [NRGN], tau), inflammatory (interleukin [IL]-6, IL-8, IL-10), and trophic (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor) proteins. Clinical outcomes were Sarnat scores of encephalopathy, seizures, MRI scores, and Bayley Scales of Infant and Toddler Development III at 15-30 months. RESULTS: Plasma NRGN, tau, IL-6, IL-8, and IL-10 were greater, whereas BDNF and vascular endothelial growth factor were lower in patients with neonatal encephalopathy vs controls. In plasma, tau, GFAP, and NRGN were directly and BDNF inversely associated with encephalopathy grade. IL-6 was inversely related to seizures. Tau was directly related to MRI abnormalities. Tau was inversely associated with Bayley Scales of Infant and Toddler Development III cognitive and motor outcomes. In CSF, NRGN was inversely associated with cognitive, motor, and language measures. GFAP, IL-6, and IL-10 were inversely related to cognitive and motor outcomes. IL-8 was inversely related to motor outcomes. CSF candidate biomarkers showed no significant relationships with encephalopathy grade, seizures, or MRI abnormalities. CONCLUSIONS: Plasma candidate biomarkers predicted encephalopathy severity, seizures, MRI abnormalities, and neurodevelopmental outcomes at 15-30 months.

C-Reactive Protein and Blood Gas Analysis in Cases of Neonatal Encephalopathy Treated with Therapeutic Hypothermia.

OBJECTIVE: Neonatal encephalopathy (NE) is one of the important causes of mortality and morbidity today. Therapeutic hypothermia (TH) applied to moderate and severe NE patients has neuroprotective effects. The role of C-reactive protein (CRP) in determining the clinical severity of NE is not clear. METHODS: Medical records of 118 NE patients treated with TH were reviewed. The patients were divided into two groups as CRP positive (CRP-P) (≥1 mg/dL) and CRP negative (CRP-N) (<1 mg/dL) according to the CRP value measured immediately before rewarming phase during TH. Cord blood base deficits (BD) and pH were also examined. RESULTS: According to Sarnat&Sarnat classification, moderate NE cases were more frequent in the CRP-N group, whereas severe cases were more frequent in CRP-P group (p<0.001). There was a significant increase in CRP value during the rewarming phase of TH in both CRP-P and CRP-N groups (p<0.001). The specificity and sensitivity for CRP (measured during TH) predicting NE severity was 72% and 77%, respectively (AUC:0.742). For cord blood BD (AUC: 0.845) 79% sensitivity and 78% specificity were found, whereas pH (AUC: 155) had 10% sensitivity and 60% specificity. CONCLUSION: CRP level measured immediately before the rewarming phase may be useful biomarker for NE severity along with cord blood BD.

Experimental evidence for alpha enolase as one potential autoantigen in the pathogenesis of both autoimmune thyroiditis and its related encephalopathy.

Alpha-enolase (ENO1) is a ubiquitous protein. Patients with autoimmune thyroiditis-associated encephalopathy have high serum ENO1Ab titers. We aimed to explore whether ENO1Ab was the pathogenic antibody in the thyroid and brain. The serum ENO1Ab titers were significantly increased in the mice immunized with Thyroglobulin (Tg). And in the mice immunized with ENO1, serum levels of both TgAb and thyroid-stimulating hormone (TSH) were significantly increased. Obvious CD16+ cell infiltration, IgG deposit and cleaved caspase-3 were observed in the thyroid of ENO1-immunized mice. Spatial learning and memory abilities and synaptic functions were impaired in ENO1-immunized mice. Furthermore, the expression levels of Iba-1, GFAP, interlukin-6, CDK5, and phosphorylated tau were increased, and endothelial tight junction proteins were decreased in the brain of ENO1-immunized mice. These results suggest that ENO1Ab can cause thyrocyte damage via ADCC effect and impair cerebral function by disrupting the blood-brain barrier.

CASPR2 autoimmunity in children expanding to mild encephalopathy with hypertension.

OBJECTIVE: To delineate autoimmune disease in association with contactin-associated protein 2 (CASPR2) antibodies in childhood, we reviewed the clinical phenotype of children with CASPR2 antibodies. METHODS: Retrospective assessment of patients recruited through laboratories specialized in autoimmune CNS disease. RESULTS: Ten children with serum CASPR2 antibodies were identified (age at manifestation 18 months to 17 years). Eight children with CASPR2 antibody titers from ≥1:160 to 1:5,120 had complex autoimmune diseases with an age-dependent clinical phenotype. Two children with structural epilepsy due to CNS malformations harbored nonspecific low-titer CASPR2 antibodies (serum titers 1:80). The clinical symptoms of the 8 children with high-titer CASPR2 antibodies were general weakness (8/8), sleep dysregulation (8/8), dysautonomia (8/8) encephalopathy (7/8), neuropathic pain (7/8), neuromyotonia (3/8), and flaccid paresis (3/8). Adolescents (3/8) showed pain, neuromyotonia, and encephalopathy, whereas younger children (5/8) displayed severe hypertension, encephalopathy, and hormonal dysfunction mimicking a systemic disease. No tumors were identified. Motor symptoms remitted with immunotherapy. Mild behavioral changes persisted in 1 child, and autism spectrum disorder was diagnosed during follow-up in a young boy. CONCLUSION: High-titer CASPR2 antibodies are associated with Morvan syndrome in children as young as 2 years. However, CASPR2 autoimmunity mimics systemic disease and hypertensive encephalopathy in children younger than 7 years. The outcome following immunotherapy was mostly favorable; long-term behavioral impairment may occur in younger children.

RNAs in Brain and Heart Diseases.

In the era of single-cell analysis, one always has to keep in mind the systemic nature of various diseases and how these diseases could be optimally studied. Comorbidities of the heart in neurological diseases as well as of the brain in cardiovascular diseases are prevalent, but how interactions in the brain-heart axis affect disease development and progression has been poorly addressed. Several brain and heart diseases share common risk factors. A better understanding of the brain-heart interactions will provide better insights for future treatment and personalization of healthcare, for heart failure patients' benefit notably. We review here emerging evidence that studying noncoding RNAs in the brain-heart axis could be pivotal in understanding these interactions. We also introduce the Special Issue of the International Journal of Molecular Sciences RNAs in Brain and Heart Diseases-EU-CardioRNA COST Action.

Neurological manifestations of COVID-19: a review of what we know so far.

Coronavirus disease 2019 (COVID-19) has become a pandemic disease globally. While it mostly presents with respiratory symptoms, it has already been found that it could manifest with a series of neurological symptoms as well, either at presentation or during the course of the disease. Symptoms vary from non-specific such as headache or dizziness to more specific such as convulsions and cerebrovascular disease (CVD). This study aims to give an overview of the neurological manifestations of COVID-19 and discuss the potential pathogenetic mechanisms of central nervous system (CNS) involvement. Clinicians and especially internists, neurologists, and infectious disease specialists should be aware of these symptoms and able to recognize them early. Prompt diagnosis and immediate management of the neurological manifestations of the novel coronavirus will not only improve the prognosis of COVID-19 patients but will also prevent the dissemination of the disease due to misdiagnosed cases.