Clinical evaluation of patients with non-aneurysmal and non-traumatic subarachnoid hemorrhage

Background: Subarachnoid haemorrhage (SAH) accounts for about 3% of all strokes and 10% of haemorrhagic strokes, with a mortality of up to 50% of cases. In 85% of cases SAH is caused by an aneurysmal rupture, 10% – are non-aneurysmal, non-traumatic, and 5% – is due to other vascular causes. The purpose of the study was the analysis of the clinical course of patients with SAH, which was not determined by rupture of aneurysm or craniocerebral trauma. Material and methods: Patients with non-traumatic and non-aneurysmal SAH hospitalized in the Institute of Neurology and Neurosurgery between 2019 and March 2021 were collected. The diagnosis was confirmed by cerebral CT and CT angiography. Results: The study included 23 patients with non-aneurysmal, non-traumatic SAH with an average age of 59.5 years, 11 women among them. The most common risk factors were: hypertension – 20, smoking – 3, diabetes – 2, obesity – 3, dyslipidemia – 2, COVID-19 – 2, autoimmune diseases – 2. Clinical manifestations included: headache (23), nausea (13), dizziness (11), damage to the cranial nerves (6), motor deficiency (4), meningeal signs (15). Most patients had Hunt-Hess grade 2 (17/23), WFNS grade 1 (16/23), Fisher score grade 1 (13/23), mRs score 2 (17/23). Five patients were placed in the Intensive Care Unit, 5 – developed vasospasm, 2 patients – died. Conclusions: Our study found that non-aneurysmal and non-traumatic SAH developed more frequently in the elderly adults with hypertension, had moderate severity and a moderate-mild post-SAH degree of disability

Diferențele genuriale la pacienții cu hemoragie subarahnoidiană non-anevrismală și non-traumatică

Department of Neurology no. 1, Nicolae Testemitanu SUMPh, Diomid Gherman Institute of Neurology and NeurosurgeryBackground. Subarachnoid haemorrhage (SHA) accounts for about 5% of all strokes, with increased mortality and morbidity. In 85% cases SHA is caused by an aneurysmal rupture, 10% of SHA are nonaneurysmal, non-traumatic, and 5% is due to other vascular causes. Objective of the study. It was the analysis of clinical evolution and prognosis, depending on gender, in patients with SHA which was not determined by rupture of aneurysm or craniocerebral trauma. Material and Methods. Patients with non-traumatic and non-aneurysmal SHA were collected, hospitalized in the Institute of Neurology and Neurosurgery “Diomid Gherman” between 2019 and March 2021. The diagnosis was confirmed by cerebral CT and CT angiography. Results. The study included 23 patients, 11 women and 12 men, with an average age of women 65.1 years and men 54.3 years. Risk factors were assessed in relation to the gender of patients: hypertension–20 (8 women and 12 men), smoking–3 men, diabetes–2 (1 women and 1 man), obesity–3 (2 women and 1 male), dyslipidemia–2 (1 male and 1 female), COVID-19–2 men, autoimmune diseases–2 men. The patient's prognosis was determined according to the scales: HuntHess grade 2 (7/11 women and 10/12 men), WFNS grade 1 (6/11 women and 10/12 men), mFisher grade 1 (4/11 women and 9/12 men), mRs score 1 (6/11 women and 11/12 men), 5–developed vasospasm (3 men and 2 women), 2 patients (women)–died. Conclusion. Non-aneurysmal, non-traumatic SHA developed more frequently in men, with lower average age than women, and multiple association of risk factors. Compared to women, men had better clinical outcomes, lower rates of complications and more favorable prognosis.Introducere. Hemoragia subarahnoidiană (HSA) reprezintă circa 5% dintre toate accidentele vasculare cerebrale, cu o mortalitate și morbiditate crescută. În 85% dintre cazuri HSA este provocată de o ruptură anevrismală, 10% – HSA este de tip non-anevrismal, non-traumatic, iar 5% – din alte cauze vasculare. Scopul lucrării. A fost efectuată analiza evoluției clinice și prognosticului în dependență de gen la pacienții cu HSA care nu a fost determinată de ruptura de anevrism sau de traumatismul cranio-cerebral. Material și Metode. Au fost selectați pacienții cu HSA non-traumatică și non-anevrismală, spitalizați în Institutul de Neurologie și Neurochirugie „Diomid Gherman”, în perioada 2019-martie 2021. Diagnosticul a fost confirmat prin CT cerebral și Angio-CT. Rezultate. În studiu au fost incluși 23 de pacienți, 11 femei și 12 bărbați, cu vârsta medie a femeilor de 65,1 ani și a bărbaților de 54,3 ani. Au fost evaluați factorii de risc în raport cu genul pacienților: HTA–20 (8 femei și 12 bărbați), fumatul – 3 bărbați, DZ – 2 (o femeie și un bărbat), obezitatea – 3 (2 femei și 1 bărbat), dyslipidemia – 2 (1 bărbat și o femeie), cu COVID-19 – 2 bărbați, cu boli autoimmune – 2 bărbați. Prognosticul conform scalelor a fost: Hunt-Hess grad 2 (7/11 femei și 10/12 bărbați), WFNS grad 1 (6/11 femei și 10/12 bărbați), mFisher grad 1 (4/11 femei și 9/12 bărbați), mRs scor 1 (6/11 femei și 11/12 bărbați), 5 – au dezvoltat vasospasm (3 bărbați și 2 femei), 2 pacienți (femei) – au decedat. Concluzii. HSA non-anevrismală, non-traumatică s-a dezvoltat mai frecvent la bărbați, cu vârsta medie mai mică decât cea a femeilor și cu mai mulți factori de risc. Comparativ cu femeile, bărbații au avut rezultate clinice mai bune, rate mai mici de complicații și prognostic mai favorabil

Факторы pиска, клиническое течение и прогноз пациентов c нон-аневризмальным и нон-травматическим cубарахноидальным кровотечением

Subarachnoid hemorrhage (SAH) accounts for about 2-7% of all strokes. In 85% cases SAH is caused by an aneurysmal rupture, 10% of SAH are non-aneurysmal, non-traumatic, and 5% of SAH is due to other causes. The risk factors with a major resonance are arterial hypertension and smoking.The purpose of the study was the analysis of the risk factors, clinical course and prognosis in patients with SAH, which was not determined by the rupture of aneurysm or craniocerebral trauma.Methods: The patients were collected during the hospitalization in the Institute of Neurology and Neurosurgery “Diomid Gherman” between 2019 and March 2021. The diagnosis was confirmed by brain CT, CT angiography and cerebral MRI. In this study, for the clinical, paraclinical evaluation and prognostic were used the Hunt-Hess, WFNS, mFisher, mRankin scales.Results: The average age of the 23 research patients is 59,85 years old. Risk factors were assessed: hypertension – 20,smoking – 3, diabetes – 2, obesity – 3, dyslipidemia–2, COVID-19 – 2, autoimmune diseases – 2. The patient’s prognosiswas determined according to the scales (medial score): Hunt-Hess grade 2 (2,39), WFNS grade 1-2 (1,78), mFisher grade1-2 (1,82), mRankin score 1-2 (1,73), 5 patients – developed vasospasm, 2 patients – died.Conclusions: SAH non-aneurysm and non-traumatic, has an almost equal gender distribution, has developed in middle-aged adult, the most common risk factor being arterial hypertension. Compared to women, men with non-anevrismaland non-traumatic SAH presented several associated risk factors, but at the same time they had good clinical results, lowcomplication rates and favorable prognosis.Hemoragia subarahnoidiană (HSA) reprezintă de la 2% până la 7% din accidentele vasculare cerebrale. În 85% HSAeste cauzată de o ruptură anevr ismală, 10% dintre HSA sunt non-anevrismale, non-traumatice, iar 5% se datorează altorcauze vasculare. Factorii de risc cu o rezonanță majoră sunt hipertensiunea arterială și fumatul.Scopul studiului a fost în a determina factorii de risc, evoluția clinică și pronosticul pacienților cu HSA non-anevrismală, non-traumatică.Metode: În perioada decembrie 2019 - martie 2021 au fost selectați 23 pacienți, spitalizați în Institutul de Neurologieși Neurochirugie “Diomid Gherman”. Diagnosticul a fost confirmat prin CT cerebral, Angio-CT și IRM cerebral, iar pentru evaluarea clinică și a pronosticului au fost utilizate scalele Hunt-Hess, WFNS, mFisher, mRankin.Rezultate: Vârsta medie a pacienților incluși în cercetare este de 59,85 ani. Factorii de risc identificați au fost:HTA–20, fumatul–3, DZ–2, obezitatea–3, dislipidemia-2, COVID-19–2, boli autoimune–2. Pronosticul relevat conformscalelor (scorul mediu) a fost: Hunt-Hess grad 2 (2,39), WFNS grad 1-2 (1,78), mFisher grad 1-2 (1,82), mRankin scor1-2 (1,73), 5 pacienți – au dezvoltat vasospasm, 2 pacienți – au decedat.Concluzii: HSA non-anevrismală și non-traumatică, a avut o distribuție egală pe sexe, s-a dezvoltat la adultul de vârstă medie, cel mai frecvent factor de risc fiind hipertensiunea arterială. Comparativ cu femeile, barbații cu HSA spontanăau prezentat o asociere din mai multi factori de risc, rate mai mici de complicații și prognostic mai favorabil.Субарахноидальное кровоизлияние (САК) составляет от 2 до 7 % от всех инсультов. В 85% САК обусловленоразрывом аневризмы, 10% САК являются неаневризмальными, не травматичными, а 5% обусловлены другимисосудистыми причинами. Основные факторы риска – это артериальная гипертония и курение.Цель исследования: определение факторов риска, клинического течения и прогноза пациентов с неаневризмальным, не травматическим САК. В период с декабря 2019 года по март 2021 года выявлены 23 пациента,госпитализированных в Институт неврологии и нейрохирургии “Диомид Герман». Диагноз был подтвержден спомощью КТ головного мозга, Ангио - КТ и МРТ головного мозга, а для клинической оценки и прогноза былииспользованы шкалы Hunt-Hess, WFNS, mFisher, mRankin.Результаты: средний возраст 23 пациентов, включенных в исследование, составляет 59,85 лет. Основнымифакторами риска были: aртериальная гипертония – 20, курение – 3, cахарный диабет – 2, ожирение – 3, дислипидемия – 2, КОВИД–19 – 2, аутоиммунные заболевания – 2. Прогноз, выявленный по шкалам (средний балл), был:Hunt-Hess 2-я степень (2,39), WFNS степень 1-2 (1,78), mFisher степень 1-2 (1,82), оценка по шкале mRankin 1-2(1,73), 5 пациентов – развили вазоспазм, 2 пациента – умерли.Выводы: неаневризмальное и нетравматическое САК встречается с одинаковой частотой как у мужчин, таки у женщин, развивается у лиц среднего возраста, наиболее частым фактором риска является артериальная гипертония. По сравнению с женщинами, мужчины со спонтанным САК имели болешь ассоциированных факторовриска, меньше осложнений и более благоприятный прогноз

Microglia jointly degrade fibrillar alpha-synuclein cargo by distribution through tunneling nanotubes

Microglia are the CNS resident immune cells that react to misfolded proteins through pattern recognition receptor ligation and activation of inflammatory pathways. Here, we studied how microglia handle and cope with alpha-synuclein (alpha-syn) fibrils and their clearance. We found that microglia exposed to alpha-syn establish a cellular network through the formation of F-actin-dependent intercellular connections, which transfer alpha-syn from overloaded microglia to neighboring naive microglia where the alpha-syn cargo got rapidly and effectively degraded. Lowering the alpha-syn burden attenuated the inflammatory profile of microglia and improved their survival. This degradation strategy was compromised in cells carrying the LRRK2 G2019S mutation. We confirmed the intercellular transfer of alpha-syn assemblies in microglia using organotypic slice cultures, 2-photon microscopy, and neuropathology of patients. Together, these data identify a mechanism by which microglia create an on-demand functional network in order to improve pathogenic alpha-syn clearance

No serological evidence for neuronal damage or reactive gliosis in neuro-COVID-19 patients with long-term persistent headache

Recent studies have indicated that long-term neurological sequelae after COVID-19 are not accompanied by an increase of canonical biomarkers of central nervous system injury in blood, but subgroup stratifications are lacking. This is a particular concern in chronic headache, which can be a leading symptom of Post-COVID diseases associated with neuronal damage such as vasculitis or autoimmune encephalitis. We here compared patients with mild Post-COVID-19 syndrome and persistent headache (persistent Post-COVID-19 headache) lasting longer than 12 weeks after the initial serological diagnosis, to patients with mild and severe COVID-19 and COVID-19-negative controls. Levels of neurofilament light chain and glial fibrillary astrocytic protein, i.e. markers of neuronal damage and reactive astrogliosis, were lower in blood from patients with persistent Post-COVID-19 headache compared to patients with severe COVID-19. Hence, our pilot serological study indicates that long-term Post-COVID-19 headache may not be a sign of underlying neuronal damage or neuroinflammation

Prediction of Function in ABCA4-Related Retinopathy Using Ensemble Machine Learning

Full-field electroretinogram (ERG) and best corrected visual acuity (BCVA) measures have been shown to have prognostic value for recessive Stargardt disease (also called “ABCA4-related retinopathy”). These functional tests may serve as a performance-outcome-measure (PerfO) in emerging interventional clinical trials, but utility is limited by variability and patient burden. To address these limitations, an ensemble machine-learning-based approach was evaluated to differentiate patients from controls, and predict disease categories depending on ERG (‘inferred ERG’) and visual impairment (‘inferred visual impairment’) as well as BCVA values (‘inferred BCVA’) based on microstructural imaging (utilizing spectral-domain optical coherence tomography) and patient data. The accuracy for ‘inferred ERG’ and ‘inferred visual impairment’ was up to 99.53 ± 1.02%. Prediction of BCVA values (‘inferred BCVA’) achieved a precision of ±0.3LogMAR in up to 85.31% of eyes. Analysis of the permutation importance revealed that foveal status was the most important feature for BCVA prediction, while the thickness of outer nuclear layer and photoreceptor inner and outer segments as well as age of onset highly ranked for all predictions. ‘Inferred ERG’, ‘inferred visual impairment’, and ‘inferred BCVA’, herein, represent accurate estimates of differential functional effects of retinal microstructure, and offer quasi-functional parameters with the potential for a refined patient assessment, and investigation of potential future treatment effects or disease progression

No evidence for neuronal damage or astrocytic activation in cerebrospinal fluid of Neuro-COVID-19 patients with long-term persistent headache

Abstract Headache is one of the most common neurological manifestations of COVID-19, but it is unclear whether chronic headache as a symptom of Post-COVID-19 is associated with ongoing CNS damage. We compared cerebrospinal fluid (CSF) levels of markers of CNS damage and inflammation in Post-COVID-19 patients with persistent headache to hospitalized acute COVID-19 patients with neurological symptoms and to non-COVID-19 disease-controls. CSF levels of neurofilament light chain, Ubiquitin carboxyl-terminal hydrolase L1 and Tau were similar in patients with persistent headache in post-COVID-19 compared to acute COVID-19 patients and all control groups. Levels of glial fibrillary astrocytic protein were lower in patients with persistent headache in post-COVID-19 compared to some control groups of patients with neurological disease. Therefore, our pilot study of CSF markers indicates that persistent post-COVID-19 headache is not a sign of underlying neuronal damage or glial activation

Brain-Derived Neurotrophic Factor in Gestational Diabetes: Analysis of Maternal Serum and Cord Blood Pairs and Comparison of Dietary- and Insulin-Dependent GDM

The Objective of our study was to investigate the influence of dietary (dGDM) and insulin-dependent (iGDM) gestational diabetes (GDM) on BDNF blood levels of corresponding maternal-neonatal pairs and compare them to pregnancies unaffected by GDM. Blood samples from 293 maternal-neonatal pairs were analyzed. Statistical analysis was performed using multiple regression analysis for association of log-transformed maternal and neonatal BDNF levels in relation to GDM, gestational age, neonatal sex, and mode of delivery. This was followed by a 2:1 matching of healthy and diabetic pairs. Maternal and neonatal BDNF levels were lowest in the iGDM group, followed by the dGDM group and healthy controls (maternal: healthy 665 ± 562 (26–2343) pg/mL vs. dGDM 593 ± 446 (25–1522) pg/mL vs. iGDM 541 ± 446 (68–2184) pg/mL; neonate: healthy 541 ± 464 (9.5–2802) pg/mL vs. dGDM 375 ± 342 (1–1491) pg/mL vs. iGDM 330 ± 326 (47–1384) pg/mL). After multiple regression analysis and additional 2:1 matching neonatal log-BDNF was significantly lower (−152.05 pg/mL, p = 0.027) in neonates of mothers with GDM compared to healthy pairs; maternal log-BDNF was also lower (−79.6 pg/mL), but did not reach significance. Our study is the first to analyze BDNF in matched maternal-neonatal pairs of GDM patients compared to a metabolically unaffected control group

Microglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes

International audienceMicroglia are crucial for maintaining brain health and neuron function. Here, we report that microglia establish connections with neurons using tunneling nanotubes (TNTs) in both physiological and pathological conditions. These TNTs facilitate the rapid exchange of organelles, vesicles, and proteins. In neurodegenerative diseases like Parkinson’s and Alzheimer’s disease, toxic aggregates of alpha-synuclein (α-syn) and tau accumulate within neurons. Our research demonstrates that microglia use TNTs to extract neurons from these aggregates, restoring neuronal health. Additionally, microglia share their healthy mitochondria with burdened neurons, reducing oxidative stress and normalizing gene expression. Disrupting mitochondrial function with antimycin A before TNT formation eliminates this neuroprotection. Moreover, co-culturing neurons with microglia and promoting TNT formation rescues suppressed neuronal activity caused by α-syn or tau aggregates. Notably, TNT-mediated aggregate transfer is compromised in microglia carrying Lrrk22(Gly2019Ser) or Trem2(T66M) and (R47H) mutations, suggesting a role in the pathology of these gene variants in neurodegenerative diseases

Comparative Analysis of Antibody Titers against the Spike Protein of SARS-CoV-2 Variants in Infected Patient Cohorts and Diverse Vaccination Regimes

The presence of neutralizing antibodies against SARS-CoV-2 correlates with protection against infection and severe COVID-19 disease courses. Understanding the dynamics of antibody development against the SARS-CoV-2 virus is important for recommendations on vaccination strategies and on control of the COVID-19 pandemic. This study investigates the dynamics and extent of α-Spike-Ab development by different vaccines manufactured by Johnson & Johnson, AstraZeneca, Pfizer-BioNTech and Moderna. On day 1 after vaccination, we observed a temporal low-grade inflammatory response. α-Spike-Ab titers were reduced after six months of vaccination with mRNA vaccines and increased 14 days after booster vaccinations to a maximum that exceeded titers from mild and critical COVID-19 and Long-COVID patients. Within the group of critical COVID-19 patients, we observed a trend for lower α-Spike-Ab titers in the group of patients who survived COVID-19. This trend accompanied higher numbers of pro-B cells, fewer mature B cells and a higher frequency of T follicular helper cells. Finally, we present data demonstrating that past infection with mild COVID-19 does not lead to long-term increased Ab titers and that even the group of previously infected SARS-CoV-2 patients benefit from a vaccination six months after the infection