Direct Neurotoxic Effect Research Articles

Drugs with a negative impact on cognitive functions (part 3): antibacterial agents in patients with chronic kidney disease.

The relationship between chronic kidney disease (CKD) and cognitive function has received increased attention in recent years. Antibacterial agents (ABs) represent a critical component of therapy regimens in patients with CKD due to increased susceptibility to infections. Following our reviewing work on the neurocognitive impact of long-term medications in patients with CKD, we propose to focus on AB-induced direct and indirect consequences on cognitive function. Patients with CKD are predisposed to adverse drug reactions (ADRs) due to altered drug pharmacokinetics, glomerular filtration decline, and the potential disruption of the blood-brain barrier. ABs have been identified as a major cause of ADRs in vulnerable patient populations. This review examines the direct neurotoxic effects of AB classes (e.g. beta-lactams, fluoroquinolones, aminoglycosides, and metronidazole) on the central nervous system (CNS) in patients with CKD. We will mainly focus on the acute effects on the CNS associated with AB since they are the most extensively studied effects in CKD patients. Moreover, the review describes the modulation of the gut microbiota by ABs, potentially influencing CNS symptoms. The intricate brain-gut-kidney axis emerges as a pivotal focus, revealing the interplay between microbiota alterations induced by ABs and CNS manifestations in patients with CKD. The prevalence of antibiotic-associated encephalopathy in patients with CKD undergoing intravenous AB therapy supports the use of therapeutic drug monitoring for ABs to reduce the number and seriousness of ADRs in this patient population. In conclusion, elucidating AB-induced cognitive effects in patients with CKD demands a comprehensive understanding and tailored therapeutic strategies that account for altered pharmacokinetics and the brain-gut-kidney axis.

Age-dependent impact of streptozotocin on metabolic endpoints and Alzheimer's disease pathologies in 3xTg-AD mice

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease with a complex origin, thought to involve a combination of genetic, biological and environmental factors. Insulin dysfunction has emerged as a potential factor contributing to AD pathogenesis, particularly in individuals with diabetes, and among those with insulin deficiency or undergoing insulin therapy. The intraperitoneal administration of streptozotocin (STZ) is widely used in rodent models to explore the impact of insulin deficiency on AD pathology, although prior research predominantly focused on young animals, with no comparative analysis across different age groups. Our study aimed to fill this gap by analyzing the impact of insulin dysfunction in 7 and 23 months 3xTg-AD mice, that exhibit both amyloid and tau pathologies. Our objective was to elucidate the age-specific consequences of insulin deficiency on AD pathology.STZ administration led to insulin deficiency in the younger mice, resulting in an increase in cortical amyloid-β (Aβ) and tau aggregation, while tau phosphorylation was not significantly affected. Conversely, older mice displayed an unexpected resilience to the peripheral metabolic impact of STZ, while exhibiting an increase in both tau phosphorylation and aggregation without significantly affecting amyloid pathology. These changes were paralleled with alterations in signaling pathways involving tau kinases and phosphatases. Several markers of blood-brain barrier (BBB) integrity declined with age in 3xTg-AD mice, which might have facilitated a direct neurotoxic effect of STZ in older mice.Overall, our research confirms the influence of insulin signaling dysfunction on AD pathology, but also advises careful interpretation of data related to STZ-induced effects in older animals.

Intereleukine-6 and Interleukine-1β levels in post-traumatic stress disorder, depression and healthy controls: a preliminary report

IntroductionPatients with Post-traumatic stress disorder (PTSD) or mood disorders, as depression, often showed dysregulation of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, resulting in increased levels of pro-inflammatory cytokines and heightened activity of the immune system that may cause alterations in the structure and function of brain regions through direct neurotoxic effects, oxidative stress, changes in levels of neurotransmitters and decreasing some neurotrophins. Among the most studied pro-inflammatory cytokines in this field there are Intereleukine-6 (IL-6) and Interleukine-1β (IL-1β); however, scant and conflicting data are currently available in the literature about their use as potential biomarkers, and even less on possible comparisons in PTSD and depression.Objectives The aim of the present study was to evaluate circulating levels of IL-6 and IL-1β in patients with PTSD and to compare them with those of subjects with depression and healthy controls.MethodsA sample of 45 subjects, including 15 subjects diagnosed with PTSD (PTSD group), 15 with depression (DEP group), and 15 healthy controls (HC group) were recruited at the Psychiatric Clinic of the Department of Clinical and Experimental Medicine, University of Pisa. HC group included subjects recruited on a voluntary basis. The psychiatric diagnosis was assessed by the Structured Clinical Interview for DSM-5-Clinician Version (SCID-5-CV), the Impact of Event Scale-Revised (IES-R) and the Trauma and Loss Spectrum-Self Report lifetime version (TALS-SR). A peripheral venous blood sample was collected to perform the biochemical assays. The analyses of IL-6 and IL-1β were performed with a dedicated enzyme-linked immunosorbent assay (ELISAs) achieved at the Laboratory of Biochemistry of the Department of Pharmacy, University of Pisa.ResultsNo statistically significant gender or age differences emerged in the three groups. There were no statistically significant differences in IL-1β levels among the three groups. Conversely, the PTSD group showed higher levels of IL-6 compared to the DEP and to the HC ones, with a statistically significant difference in the post-hoc analysis among the PTSD and DEP groups with respect to the HC one (p<0.05).ConclusionsOur results suggest the key role of a chronic low-grade inflammatory state in PTSD and in depression, probably related to a dysregulation in HPA axis and cortisol release, with an increase in proinflammatory cytokines including IL-6 that seemed to be more pronounced in PTSD.Disclosure of InterestNone Declared

The Role of Alcohol Use Disorders in the Development and Progression of Dementia

IntroductionIn recent years, there has been an increase in interest and research into the link between alcohol use disorders (AUD) and dementia. Alcohol use disorders, which are characterised by excessive and problematic alcohol consumption, have been associated to a variety of detrimental health effects, including liver disease, cardiovascular difficulties, and cognitive impairments.ObjectivesTo explore the link between alcohol use disorders and dementia onset and progression, explaining probable causes and emphasising preventive approaches.Methods The present study involved a thorough examination of relevant research papers, with a specific emphasis on longitudinal cohort studies, neuropathological observations, and biochemical interactions pertaining to the effects of alcohol on the brain. In addition to the aforementioned criteria, the review also took into account other complicating factors, including choices regarding lifestyle, genetic predisposition, and coexisting medical conditions.Results The results indicate a strong association between prolonged and excessive alcohol consumption and a heightened susceptibility to the early onset of dementia. The mechanisms underlying alcohol-related neurological damage encompass direct neurotoxic effects of alcohol, thiamine shortage, and alcohol-related cerebrovascular illness. Moreover, it is worth noting that alcohol use disorder (AUD) has the potential to worsen the advancement of neurodegenerative processes in individuals already diagnosed with dementia.ConclusionsThe association between AUD (Alcohol Use Disorder) and dementia is complex and involves multiple factors, presenting considerable difficulties in terms of clinical intervention and treatment. The use of early intervention strategies and public health initiatives focused on addressing alcohol use disorder (AUD) could have a significant impact on preventing or reducing the development of dementia.Disclosure of InterestNone Declared

Hymenoptera sting as atypical causative factor for Guillain Barré Syndrome and chronic inflammatory demyelinating polyneuropathy – A case report and insights on pathophysiology

Introduction. Neurological manifestations secondary to Hymenoptera stings are rare. However, the literature describes cases of severe central and peripheral nervous system damage. Suspected pathophysiological mechanisms include hypoxic-ischemic damage, demyelination, and the direct neurotoxic effect of venoms. In this context, bee stings could be a possible atypical causative factor for Guillan–Barré syndrome and chronic inflammatory demyelinating polyneuropathy. Case report. We present the case of a 32-year-old patient who declared the presence of a bee sting two weeks before the onset of neurological manifestations (flaccid quadriparesis, predominantly distal, with paresthesia at the same level) that were initially diagnosed as a Guillain Barré syndrome. Despite the treatment with immunoglobulins in the acute phase, the worsening of the motor deficit after one month required a new course of immunoglobulins, associating corticosteroids, with initially favorable evolution. However, the presence of a new relapse after eight weeks, correlated with changes such as albumin-cytological dissociation in the examination of the cerebrospinal fluid and the appearance of active denervation on the electroneuromyography study, established the final diagnosis of chronic inflammatory demyelinating polyneuropathy. Conclusions. We consider the presented case proof of the relationship between the Hymenoptera sting and various peripheral nervous system pathologies. Inflammatory and demyelinating changes common to Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy appear to be the primary pathophysiological mechanism to explain this uncommon correlation.

Generalized myoclonus restricted to the “Smack” withdrawal state: A rare case report

Myoclonus is regarded as a direct neurotoxic effect of opioid metabolites. It is seen less frequently in conjunction with opioid discontinuation (opioid withdrawal myoclonus [OWM]). Only a few case reports from palliative medicine and anesthesia have highlighted the development of OWM. We report an unusual case of a 35 years old, opioid-dependent (smack) adult male who developed abnormal involuntary jerky movements of limbs and torso in the withdrawal phase. There was no change in the level of consciousness. The neurological examination as well as serum biochemistry was normal. The electroencephalogram showed no epileptiform activity. The patient was started on oral substitution therapy (tramadol 150 mg/day) after which abnormal movements subsided within 72 h. We conclude that myoclonus can be a part of opioid withdrawal. Appropriate recognition of its benign nature and psycho-education to patients and families shall foresee better outcomes.

Neurotoxicity and Outcomes from Developmental Lead Exposure: Persistent or Permanent?

Childhood lead poisoning remains an important public health issue in the United States, as well as elsewhere in the world. Although primary prevention is a major goal and it is critically important to keep children from getting poisoned, it is also important to explore ways to reduce the neurotoxic effects of lead in those children already poisoned. Whether lead-induced neurotoxicity and its related adverse outcomes are viewed as "permanent" or "persistent" may influence the way in which potential remediation efforts are considered for improving outcomes from childhood lead poisoning. The objective of this commentary was to discuss the ideas of permanence and persistence in relation to the direct neurotoxic effects of lead on the brain and the resulting adverse outcomes from these effects. Recent new insights regarding potential mitigation of lead-induced neurotoxic effects on brain and behavior are considered along with clinical information on neurorehabilitation to suggest potential strategies for improving cognitive/behavioral outcomes in lead-poisoned children. The distinction between permanent and persistent in regard to lead-induced neurotoxicity and its resulting outcomes may have broad implications for public health policies in response to the problem of childhood lead exposure. The term permanent implies that the damage is irreversible with little chance of improvement. However, there is evidence that at least some of the adverse cognitive/behavioral outcomes from lead exposure are persistent rather than permanent and potentially amenable, under the appropriate circumstances, to some level of mitigation. This author recommends that clinical, interventional research efforts be devoted to exploring optimal neurorehabilitative and enrichment conditions to stimulate plasticity and enhance functioning to determine the extent to which promising results from preclinical studies of lead-induced brain damage and the mitigation of these effects can be successfully translated to humans. https://doi.org/10.1289/EHP12371.

Time- and Concentration-Dependent Adverse Effects of Paclitaxel on Non-Neuronal Cells in Rat Primary Dorsal Root Ganglia.

Paclitaxel is a chemotherapeutic agent used to treat a wide range of malignant tumors. Although it has anti-tumoral properties, paclitaxel also shows significant adverse effects on the peripheral nervous system, causing peripheral neuropathy. Paclitaxel has previously been shown to exert direct neurotoxic effects on primary DRG neurons. However, little is known about paclitaxel's effects on non-neuronal DRG cells. They provide mechanical and metabolic support and influence neuronal signaling. In the present study, paclitaxel effects on primary DRG non-neuronal cells were analyzed and their concentration or/and time dependence investigated. DRGs of Wister rats (6-8 weeks old) were isolated, and non-neuronal cell populations were separated by the density gradient centrifugation method. Different concentrations of Paclitaxel (0.01 µM-10 µM) were tested on cell viability by MTT assay, cell death by lactate dehydrogenase (LDH) assay, and propidium iodide (PI) assay, as well as cell proliferation by Bromodeoxyuridine (BrdU) assay at 24 h, 48 h, and 72 h post-treatment. Furthermore, phenotypic effects have been investigated by using immunofluorescence techniques. Paclitaxel exhibited several toxicological effects on non-neuronal cells, including a reduction in cell viability, an increase in cell death, and an inhibition of cell proliferation. These effects were concentration- and time-dependent. Cellular and nuclear changes such as shrinkage, swelling of cell bodies, nuclear condensation, chromatin fragmentation, retraction, and a loss in processes were observed. Paclitaxel showed adverse effects on primary DRG non-neuronal cells, which might have adverse functional consequences on sensory neurons of the DRG, asking for consideration in the management of peripheral neuropathy.

Нейротоксическое действие этанола и других психоактивных веществ как общепатологическое основание токсической энцефалопатии

The purpose of the paper was to establish pathomorphological changes in human brain structures in chronic alcohol and combined (alcohol consumed with surrogates, psychoactive, and medicinal substances) intoxication and the possibility of their differential diagnosis. Materials and methods. The following were studied in detail: sensorimotor cortex, medulla oblongata, cerebellum, thalamus, substantia nigra, as well as pericellular and perivascular oedemata in persons who had died from chronic alcohol or combined intoxication, according to 140 forensic medical examination reports and medical history with histological and pathomorphological data. In the cortex, medulla oblongata, and cerebellum, severe pathological forms of neurons (anucleated cells, shadow cells, and dark cells) were selectively studied and counted. Homeostasis parameters in the microcirculatory bed were examined. As controls, we used data of people who had died as a result of various injuries that caused shock or blood loss. Staining was performed with haematoxylin and eosin, according to Nissl and according to Spielmeyer. The results of the research showed that in combined intoxication, the lungs are involved in the pathological process. The number of affected neurons in the brainstem, cerebral cortex, and cerebellum in combined intoxication was statistically significantly higher than that in the control samples. This pathology was also observed in chronic alcohol intoxication; however, the difference from the control samples was insignificant. In chronic alcohol intoxication, the cardiac type of thanatogenesis in the form of alcoholic cardiomyopathy prevails, while in combined intoxication, the pulmonary-cerebral and cerebral types of thanatogenesis are more common. Changes in the brain in combined intoxication are mainly the result of impaired haemodynamics of the microcirculatory bed in the alveoli, as well as of a direct neurotoxic effect of ethanol on the brain; thanatogenesis in this case is pulmonary-cerebral.

Neuropathologic Features in Chronic Methamphetamine Use.

Methamphetamine is a psychostimulant that exerts its euphoric and stimulant effects by increasing cytosolic monoamine concentration at the nerve terminal. In addition to its known systemic cardiovascular effects, there is compelling evidence to suggest a direct neurotoxic effect of methamphetamine; however, the existing body of literature includes very few human tissue studies. This exploratory analysis used postmortem human brain specimens to examine histologic and immunohistochemical features associated with chronic methamphetamine use. This retrospective cohort study included 60 decedents who were autopsied at the University of Iowa Hospitals and Clinics between the years 2015 and 2021. Logistic regression models demonstrated no definite pathologic changes in the hippocampi of individuals with a history of chronic methamphetamine use. Decedents with a history of methamphetamine use had a marginally increased odds of basal ganglia arteriosclerosis, which did not reach statistical significance (odds ratio, 3.33; 95% confidence interval, 0.6-19.2; P = 0.17), which may be independent of the systemic hypertensive effects of methamphetamine. Future studies that include targeted examination of brain regions of interest, such as the basal ganglia and specifically the striatum, may prove revealing.

Cognitive impairment in patients with coronavirus infection

The pathogenesis of the development of cognitive impairment (CI) associated with the SARS-CoV-2 virus is complex and includes the direct neurotoxic effect of the virus, vascular, disimmune factors, artificial lung ventilation, and adverse psychological consequences of social isolation. The relationship between CI and SARS-CoV-2 infection appears to be two-way: patients with premorbid CI have a higher risk of infection, severe illness, and death; on the other hand, past infection with SARS-CoV-2 may stimulate the clinical onset and progression of CI, including Alzheimer's disease. For the treatment of severe CI after COVID-19, memantine (akatinol memantine) is recommended.

Serum neurofilament light chain levels in Covid-19 patients without major neurological manifestations.

BackgroundIncreased serum levels of neurofilament light chain (sNFL), a biomarker of neuroaxonal damage, have been reported in patients with Covid-19. We aimed at investigating whether sNFL is increased in Covid-19 patients without major neurological manifestations, is associated with disease severity, respiratory and routine blood parameters, and changes longitudinally in the short term.MethodssNFL levels were measured with single molecule array (Simoa) technology in 57 hospitalized Covid-19 patients without major neurological manifestations and in 30 neurologically healthy controls. Patients were evaluated for PaO2/FiO2 ratio on arterial blood gas, Brescia Respiratory Covid Severity Scale (BRCSS), white blood cell counts, serum C-reactive protein (CRP), plasma D-dimer, plasma fibrinogen, and serum creatinine at admission. In 20 patients, NFL was also measured on serum samples obtained at a later timepoint during the hospital stay.ResultsCovid-19 patients had higher baseline sNFL levels compared to controls, regardless of disease severity. Baseline sNFL correlated with serum CRP and plasma D-dimer in patients with mild disease, but was not associated with measures of respiratory impairment. Longitudinal sNFL levels tended to be higher than baseline ones, albeit not significantly, and correlated with serum CRP and plasma D-dimer. The PaO2/FiO2 ratio was not associated with longitudinal sNFL, whereas BRCSS only correlated with longitudinal sNFL variation.ConclusionsWe provide neurochemical evidence of subclinical axonal damage in Covid-19 also in the absence of major neurological manifestations. This is apparently not fully explained by hypoxic injury; rather, systemic inflammation might promote this damage. However, a direct neurotoxic effect of SARS-CoV-2 cannot be excluded.

Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia.

(1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery embolism and myocardial infarction with a recent stroke. In this translational study, we evaluated whether rt-PA treatment after experimental ischemic stroke with or without additional hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old infarct area. (2) In total, 72 male C57BL/6N mice were used. Ischemic stroke (index stroke) was induced by transient middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index stroke to determine whether a recent ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop hyperglycemia were pre-treated with streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, p = 0.02; at 14 days, p = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (p = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial hemorrhages could be detected. (4) Thrombolysis after recent ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However, hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role.

Neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia: Experience from a tertiary care center in India.

Data of neurocognitive deficits in survivors of acute lymphoblastic leukemia (ALL) is scarce from low middle-income countries (LMICs), and is influenced by biological and cultural variations. The objective of this study was to assess the prevalence and spectrum of neurocognitive deficits in a cohort of survivors from India. Seventy survivors of childhood ALL were evaluated for neurocognitive deficits by the Indian adaptation of Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IVINDIA ). The prevalence of neurocognitive deficits was calculated based on the full-scale intelligence quotient (FSIQ), and scores in discrete domains like verbal comprehension, perceptual reasoning, working memory, and processing speed were calculated and compared to demographics, treatment, and sociocultural factors. The mean (SD) current age and time since diagnosis was 10.5 (±3.2) years and 5 (±2.8) years, respectively. The mean FSIQ was 86.1 ± 20.5, with significant neurocognitive deficit (FSIQ <90) being prevalent in 50% (95% CI: 38%-62%) of the cohort. The proportion of survivors with deficits in individual domains of verbal comprehension, perceptual reasoning, working memory, and processing speed were 49%, 50%, 47%, and 44%, respectively. The odds of having neurocognitive deficits were higher when a child belonged to lower socioeconomic strata (OR 5.7, p=.004), parents with lower education attainment (OR 4.3, p=.041), and whose birth order was higher (OR 20.1, p=.005). Age at diagnosis/assessment, chemotherapy received, or dose of radiotherapy did not have a direct impact on neurocognition. Rates of neurocognitive deficits are higher in survivors in LMICs, with socioeconomic variables contributing more than the direct neurotoxic effects of treatment.

P02 Doctor, I just don't feel alright

P02 Doctor, I just don't feel alright

An Atypical Case of Mild COVID-19 Infection with Severe Guillain-Barré Syndrome as Neurological Manifestation

Abstract Introduction More than 80 million people have been infected with coronavirus disease 2019 (COVID-19) infection worldwide till date with more than 17,00000 fatalities. Although COVID-19 commonly affects respiratory system in the form of cough and dyspnea, a neurotropic presentation has been described in one-third of patients. Objective We report an atypical case of COVID-19 with mild symptoms who presented to our hospital with features suggestive of severe Guillain-Barré syndrome (GBS). Discussion The mechanisms by which severe acute respiratory syndrome coronavirus 2 causes neurologic damage are multifactorial, including direct damage to specific receptors, cytokine-mediated injury, secondary hypoxia, and retrograde travel along nerve fibers. The pathogenesis of GBS secondary to COVID-19 is not yet well understood. It is hypothesized that viral illnesses-related GBS could be mediated due to autoantibodies or direct neurotoxic effects of viruses. Conclusion In this ongoing era of pandemic, it is very important for the clinicians to be aware of association of GBS with COVID-19, as early diagnosis and treatment of this complication could have gratifying results. It is also very important to differentiate GBS from critical illness neuropathy and respiratory distress secondary to COVID-19 itself, as treatment to the above conditions is quite different and inability to correctly diagnose could lead to significant increase in morbidity and mortality.

Alcohol-related dementia – an overlooked entity?

IntroductionThe relationship between alcohol use and dementia is complex. There is a J-shaped relationship between alcohol use and cognitive impairment and evidence shows that one-quarter of the dementia population have alcohol related problems. It is estimated that alcohol-related dementia (ARD) contributes for about 10% of all cases of dementia, especially early-onset dementia, but is largely overlooked or seen as a comorbid factor.ObjectivesTo clarify the relationship between alcohol use, alcohol-related brain damage and dementia; to review the clinical features, neuropathology, nosology and neuropsychology of ARD and alcohol-induced persisting amnestic syndrome (Wernicke-Korsakoff syndrome- WKS).MethodsWe performed a review of systematic reviews from the last 10 years. A total of 28 systematic reviews were identified.ResultsHeavy alcohol use has been shown to be a contributory factor and necessary factor in the development of multiple brain diseases. It may cause brain damage in multiple ways: direct neurotoxic effect of acetaldehyde; thiamine deficiency. It is also a risk factor for other conditions, such as hepatic encephalopathy, epilepsy and head injury.ConclusionsClinical observation favors the diagnosis of ADR as a distinct entity, but broader evidence reflects significant commonality between ARD and WKS, tough neuropsychological studies have largely attempted to differentiate these syndromes. Repeated episodes of WKS may cause cognitive deterioration. In contrast to other common causes of dementia, the decline in cognitive functioning in ARD is relatively non-progressive if abstinence is maintained, or even partially reversible, as supported by neuroimaging evidence. Given the increase in per capita consumption, it is expected a disproportionate increase in ARD.

Mercury and neurochemical biomarkers in multiple brain regions of five Arctic marine mammals

Mercury is a neurotoxic chemical that represents one of the greatest pollution threats to Arctic ecosystem health. Evaluating the direct neurotoxic effects of mercury in free ranging wildlife is challenging, necessitating the use of neurochemical biomarkers to assess potential sub-clinical neurological changes. The objective of this study was to characterize the distribution and speciation of mercury, as well as exposure-associated changes in neurochemistry, across multiple brain regions (n = 10) and marine mammal species (n = 5) that each occupy a trophic niche in the Arctic ecosystem. We found consistent species differences in mean brain and brain region-specific concentrations of total mercury (THg) and methyl mercury (MeHg), with higher concentrations in toothed whales (narwhal, pilot whales and harbour porpoise) compared to fur-bearing mammals (polar bear and ringed seal). Mean THg (μg/g dw) in decreasing rank order was: pilot whale (11.9) > narwhal (7.7) > harbour porpoise (3.6) > polar bear (0.6) > ringed seal (0.2). The higher THg concentrations in toothed whales was associated with a marked reduction in the percentage of MeHg (<40 %) compared to polar bears (>70 %) that had lower brain THg concentrations. This pattern in mercury concentration and speciation corresponded broadly to an overall higher number of mercury-associated neurochemical biomarker correlations in toothed whales. Of the 226 correlations between mercury and neurochemical biomarkers across brain regions, we found 60 (27 %) meaningful relationships (r>0.60 or p < 0.10). We add to the growing weight of evidence that wildlife accumulate mercury in their brains and demonstrate that there is variance in accumulation across species as well as across distinct brain regions, and that some of these exposures may be associated with sub-clinical changes in neurochemistry.

Astenic disorders within the framework of post-covid syndrome

The direct neurotropic and neurotoxic effect of the SARS-CoV-2 virus on the central nervous system, as well as the stressful effect of various factors of the COVID-19 pandemic, contribute to the development of the so-called post-COVID syndrome. The clinical picture of the syndrome includes asthenic, anxiety-asthenic, and depressive manifestations. When prescribing psychopharmacotherapy to patients who have undergone COVID-19, it is recommended to assess the potential benefits and risks in the aspect of using drugs not only with therapeutic antiasthenic and anxiolytic properties, but with minimally expressed undesirable effects and adverse drug interactions.

Neurological complications of hepatitis C infections

Die chronische Hepatitis-C-Virus(HCV)-Infektion ist eine hochprävalente Systemerkrankung, die verschiedene neurologische Komplikationen verursachen kann. Es lassen sich HCV-assoziierte Symptome im zentralen und peripheren Nervensystem sowie der Muskulatur unterscheiden. Wichtige Pathomechanismen sind die HCV-assoziierte Autoimmunität (z. B. gemischte Kryoglobulinämie mit Polyneuropathie) und direkte Neurotoxizität (z. B. bei HCV-assoziierten kognitiven Defiziten). Die häufigsten neurologischen Komplikationen sind distal-symmetrische Polyneuropathien, Small-fiber-Neuropathien und kognitive Defizite. Die HCV-Infektion stellt außerdem einen Risikofaktor für ischämische und hämorrhagische Schlaganfälle sowie den Morbus Parkinson dar. Die frühe Identifikation und antivirale Behandlung HCV-positiver Patienten steht im Zentrum der Behandlung. Durch neue antivirale Therapien können >90 % der Patienten dauerhaft von der HCV-Infektion geheilt werden.