Search Results (406)

Complete or partial loss of smell (anosmia), sometimes in association with distorted olfactory perceptions (parosmia), is a common neurological symptom affecting nearly 60% of patients suffering from post-acute neurological sequelae of COronaVIrus Disease of 2019 (COVID-19) syndrome, called long COVID. Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) may gain access from the nasal cavity to the brain (neurotropism), and the olfactory route has been proposed as a peripheral site of virus entry. COVID-19 is a risk factor for developing Alzheimer’s Disease (AD), an age-dependent and progressive neurodegenerative disorder characterized in affected patients by early olfaction dysfunction that precedes signs of cognitive decline associated with neurodegeneration in vulnerable brain regions of their limbic system. Here, we summarize the recent literature data supporting the causal correlation between the persistent olfactory deterioration following SARS-CoV-2 infection and the long-delayed manifestation of AD-like memory impairment. SARS-CoV-2 infection of the olfactory neuroepithelium is likely to trigger a pattern of detrimental events that, directly and/or indirectly, affect the anatomically interconnected hippocampal and cortical areas, thus resulting in tardive clinical dementia. We also delineate future advancement on pharmacological and rehabilitative treatments to improve the olfactory dysfunction in patients recovering even from the acute/mild phase of COVID-19. Collectively, the present review aims at highlighting the physiopathological nexus between COVID-19 anosmia and post-pandemic mental health to favor the development of best-targeted and more effective therapeutic strategies in the fight against the long-term neurological complications associated with SARS-CoV-2 infection. Full article

Influenza is typically framed as an acute respiratory infection, yet accumulating evidence suggests that—like SARS-CoV-2—it may trigger persistent, multi-organ morbidity consistent with a post-acute infection syndrome (“long flu”). Leveraging the nationwide FinnGen registry infrastructure, we conducted a temporally stratified disease-wide association study (DWAS) to map antecedent risk factors and long-term sequelae following clinically diagnosed influenza and COVID-19. We assembled an exposed cohort comprising 9204 individuals with influenza (ICD-10 J09–J11) and 4258 individuals with COVID-19 (ICD-10 U072) recorded in specialist inpatient/outpatient care between 1998 and 2021, and an unexposed comparator cohort of 420,005 individuals with no recorded influenza or pneumonia (J09–J18) across their available medical history. Across harmonized clinical endpoints, we fitted age- and sex-adjusted Cox proportional hazards models and controlled for multiple testing using a stringent false discovery rate threshold (FDR-adjusted p < 0.001), further interrogating temporal persistence within 1-, 5-, and 15-year windows. The DWAS revealed that both infections are associated with broad, system-spanning disease signatures extending beyond the respiratory tract, including circulatory, neurological, metabolic, musculoskeletal, digestive, mental/behavioural, ocular, and oncologic endpoints. Predisposition analyses demonstrated that infection risk is concentrated in individuals with substantial pre-existing multimorbidity, most prominently cardiovascular disease, alongside cardiometabolic, respiratory, renal, neuropsychiatric, and inflammatory conditions. Post-infection analyses identified a durable burden of incident multi-system morbidity after influenza, with particularly robust and persistent cardiovascular and neurological signatures—encompassing thromboembolic disease and major adverse cardiovascular outcomes, as well as migraine, neurodegenerative disorders, and depression—together with metabolic and renal sequelae that, in subsets, extended across multi-year horizons. Collectively, these longitudinal findings reframe influenza as a systemic event embedded within a chronic disease continuum, motivate recognition of “long flu” as a clinically meaningful post-viral risk landscape, and support intensified prevention and risk-stratified surveillance strategies alongside analogous efforts for long COVID. Full article

Background and Clinical Significance: Overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) in children is a rare but life-threatening metabolic emergency. The coexistence of hyperosmolality and ketoacidosis increases neurologic vulnerability and complicates fluid and insulin management. Early identification and osmolality-guided therapy are essential to prevent cerebral edema and other complications. This case describes a 5-year-old boy with new-onset type 1 diabetes mellitus (T1D) presenting with DKA/HHS overlap two weeks after influenza vaccination—an unusual temporal association without proven causality. Case Presentation: A previously healthy 5-year-old presented with progressive polyuria, polydipsia, nocturnal enuresis, fatigue, and drowsiness. Two weeks earlier, he had received the influenza vaccine. Examination revealed moderate dehydration without Kussmaul respiration or altered consciousness. Laboratory evaluation showed glucose 45.9 mmol/L (826 mg/dL; reference 3.9–7.8 mmol/L), venous pH 7.29 (reference 7.35–7.45), bicarbonate 12 mmol/L (reference 22–26 mmol/L), moderate ketonuria, and measured serum osmolality 344 mOsm/kg (reference 275–295 mOsm/kg), fulfilling diagnostic criteria for DKA/HHS overlap. After an initial 20 mL/kg 0.9% NaCl bolus, fluids were adjusted to maintenance plus approximately 10% deficit using 0.45–0.75% NaCl according to sodium/osmolality trajectory. Intravenous insulin (approximately 0.03–0.05 IU/kg/h) was initiated once blood glucose no longer decreased adequately with fluids alone and had stabilized near 22.4 mmol/L (≈400 mg/dL). Dextrose was added when glucose reached 13.9 mmol/L (250 mg/dL) to avoid rapid osmolar shifts. Hourly neurological and biochemical monitoring ensured a glucose decline of 2.8–4.2 mmol/L/h (50–75 mg/dL/h) and osmolality decrease ≤3 mOsm/kg/h. The patient recovered fully without cerebral edema or neurologic sequelae. IA-2 antibody positivity with low C-peptide and markedly elevated HbA1c confirmed new-onset T1D. Conclusions: This case highlights the diagnostic and therapeutic challenges of pediatric DKA/HHS overlap. Osmolality-based management, conservative insulin initiation, and vigilant monitoring are crucial for preventing complications. The temporal proximity to influenza vaccination remains incidental. Full article

COVID-19 has raised significant concern regarding its neurological impact, particularly during the early pandemic waves when severe systemic inflammation and neuroimmune dysregulation were more common. Although SARS-CoV-2 has been extensively studied, the precise mechanisms underlying its neurological effects remain incompletely understood, and much of the available evidence is derived from early variants with higher pathogenicity. Current research indicates that neuroinflammatory processes—driven primarily by systemic cytokine elevation, microglial activation, and blood–brain barrier dysfunction—contribute to a wide range of neurological symptoms. Severe complications such as encephalopathy, stroke, and cognitive impairment were predominantly reported in critically ill patients infected with the Wuhan, Alpha, or Delta variants, while such manifestations are considerably less frequent in the Omicron era. Most proposed mechanisms, including ACE2-mediated viral entry into the central nervous system, are supported mainly by experimental or preclinical studies rather than definitive human evidence. Biomarkers such as IL-6 and TNF-α, along with neuroimaging modalities including MRI and PET, offer useful but indirect indicators of neuroinflammation. Therapeutic approaches continue to focus on controlling systemic inflammation through immunomodulatory agents, complemented by targeted non-pharmacological strategies—such as physical rehabilitation, cognitive support, and psychological interventions—for the minority of patients with persistent neurological deficits. Overall, current evidence supports a variant-dependent neuroinflammatory profile and underscores the need for longitudinal, mechanism-focused studies to better characterize long-term neurological outcomes and refine therapeutic strategies. Full article

Background/Objectives: Edwardsiella tarda is a rare Gram-negative pathogen that uncommonly infects humans. Neonatal infections are extremely rare but often severe, with a high incidence of central nervous system (CNS) complications. Case presentation: We report a term neonate born via spontaneous vaginal delivery who developed systemic signs of infection within 18 h of life. Blood and cerebrospinal fluid (CSF) cultures grew Edwardsiella tarda. CSF analysis revealed severe meningoencephalitis. Maternal stool culture was also positive for E. tarda, suggesting vertical transmission. Despite initial systemic antibiotic therapy with ampicillin, gentamicin, and ceftriaxone, neuroimaging revealed progressive multifocal brain abscesses. The infant underwent a series of neurosurgical procedures, including bilateral drainage of abscesses, Rickham reservoir placement and ventriculoperitoneal shunting. A revised antibiotic regimen, including systemic meropenem and trimethoprim-sulfamethoxazole plus intrathecal gentamicin, was administered. At six months, the infant showed mild motor delay with lower limb hypertonia and was under close neurosurgical and developmental follow-up. Methods: We conducted a literature review of 12 published neonatal E. tarda infections, including our case. Results: Most infected infants presented within 72 h of life and exhibited CNS involvement. Mortality was 25%, and 44% of survivors experienced long-term neurologic sequelae. Conclusions: Edwardsiella tarda infection in neonates is rare but potentially devastating. Early suspicion, culture confirmation, aggressive antibiotic therapy, and multidisciplinary care, including neurosurgical management, are essential for improving outcomes. Full article

Background: Posteriorly directed aneurysms at the internal carotid–posterior communicating artery (ICA–PCoA) junction concentrate technical risk at the posteromedial neck where the PCoA origin and perforators exist beneath the optic apparatus. Our aim was to describe, in a reproducible fashion, an anatomy-driven sequence in the management of a ruptured ICA–PCoA aneurysm that visualized the posterior wall and a closing line parallel to the PCoA axis and which is placed within contemporary practice. Case Presentation: This is a single case study employing predetermined surgical techniques demonstrating a reproducible method of anatomical microsurgery applied to a posterior projecting ICA-PCoA aneurysm. The authors describe a 62-year-old female who was stabilized by nimodipine and aggressive blood pressure control in the systolic range 140–160 mmHg after an aneurysmal subarachnoid hemorrhage. Diagnostic contrast catheter angiography showed a left ICA-PCoA aneurysm of 13.1 × 10.0 mm at the base with a neck of 4.3 mm projecting posteriorly into the carotid–optic cistern. Complete adherence to a protocol of staged techniques was employed for the operation, as detailed below. Step 1: Early cisternal decompression requiring total and immediate relaxation of the temporal lobe, rapidly opening up the carotid–optic anatomical window. Step 2: Circumferential dissection about the neck of the aneurysm permitting definition of the true posteromedial wall and definition of the perforator territories and anterior choroidal territories. Step 3: Brief but effective ICA proximal quiescence (58 s) permitting clipping under direct vision. Step 4: Staged closure of two clips with the closing line of the clips orientated parallel to the axis of the PCoA with maintenance of the diameter of all parent vessels, the origin of the PCoA and the integrity of the perforators. Urgent postoperative digital subtraction angiography (DSA) study showed complete exclusion of the aneurysm with no alteration in flow characteristics, and 3 months later DSA studies again showed permanent obliteration and patency of those branches. The immediate DSA demonstrated complete exclusion of the aneurysm with patent supraclinoid ICA caliber and PCoA ostium, the anterior choroidal artery was preserved; no angiographic vasospasm was identified. The postoperative course was uncomplicated; there was no hydrocephalus, seizure disorder or delayed ischemia. At discharge and three months postprocedure the patient was neurologically intact (Modified Rankin Scale 0). Non-contrast cranial CT (three months) demonstrated stable clip position and no hemorrhagic or ischemic sequelae. Conclusions: In posteriorly projecting ICA–PCoA aneurysms that are disturbed beneath the optic apparatus, an anatomy-guided strategy—early cisternal decompression, true posteromedial neck exposure, brief purposeful quieting of the proximal ICA and two-clip closure parallel to the PCoA in selected cases—may provide the opportunity for durable occlusion whilst the physiology of branching is preserved. We intend for this transparent description to be adopted, refined or discarded based on local anatomy and practice. Full article

Posterior Reversible Encephalopathy Syndrome (PRES) is a rare but potentially reversible neurological manifestation associated with Multisystem Inflammatory Syndrome in Children (MIS-C). We report an eight-year-old boy who developed PRES secondary to MIS-C following asymptomatic SARS-CoV-2 exposure. The patient presented with fever, seizures, decreased consciousness, and visual disturbances. MRI revealed characteristic bilateral parieto-occipital and posterior temporal cortical–subcortical hyperintensities, while CT scans were normal. The patient achieved full neurological recovery with corticosteroid therapy, blood pressure control, and supportive management. This case underscores the importance of early MRI in detecting PRES when clinical or CT findings are inconclusive, emphasizing the need for heightened awareness among pediatric clinicians to prevent irreversible neurological sequelae. Full article

Background: Adrenomedullin (ADM) is a multifunctional peptide with vasoregulatory, antimicrobial, and anti-inflammatory properties. Its stable fragment, mid-regional pro-adrenomedullin (MR-proADM), is a validated biomarker in sepsis and systemic infections, but its role in viral neuroinfections remains unexplored. Tick-borne encephalitis (TBE), caused by the tick-borne encephalitis virus (TBEV), is a major viral infection of the central nervous system (CNS) associated with long-term neurological sequelae. This study aimed to assess MR-proADM levels in cerebrospinal fluid (CSF) and serum of patients with TBE and to evaluate their diagnostic utility and pathophysiological significance. Methods: This retrospective observational study included 20 patients with confirmed TBE and 14 non-infectious neurological controls. MR-proADM concentrations were measured in paired CSF and serum samples using an ELISA assay. Statistical analyses included group comparisons (Mann–Whitney U test), correlation analyses (Spearman’s r), and receiver operating characteristic (ROC) curve evaluation. Results: Serum MR-proADM levels at baseline (SER1) were significantly lower in TBE patients compared with controls (p = 0.0197). The CSF/serum MR-proADM ratio differed significantly between groups (p = 0.0063) and showed the best diagnostic performance (AUC = 0.816, 95% CI 0.63–0.93; sensitivity 79%, specificity 80%). MR-proADM concentrations in CSF correlated with total CSF protein (r = 0.53), suggesting an association with blood–CSF barrier dysfunction. Strong reproducibility was observed for serum MR-proADM between sampling points (r = 0.83). Conclusions: MR-proADM levels in CSF and serum are altered in patients with TBE, indicating its potential as a biomarker of CNS infection and inflammation. The CSF/serum MR-proADM ratio may serve as a sensitive indicator of blood–CSF barrier involvement, while decreased serum levels may reflect impaired systemic neuroprotective response. These findings highlight a possible role of ADM in neuroimmune regulation during viral encephalitis and warrant validation in larger prospective studies. Full article

Central nervous system (CNS) infections caused by Salmonella species (spp.) are exceptionally rare in adults but are associated with significant morbidity and mortality, particularly in immunocompromised individuals. Clinical presentation is often nonspecific, including fever, headache, or altered mental status, while imaging may demonstrate meningeal enhancement, abscesses, or cytotoxic lesions. We present a systematic review of non-typhoidal Salmonella spp. infections involving the CNS across various immunosuppressive contexts, illustrated by the case of a 38-year-old HIV-positive man with well-controlled infection. He developed disseminated Salmonella enterica infection, with bacteremia, septic arthritis, and ultimately corpus callosum involvement, following chronic self-administration of corticosteroids for cluster headaches. This case underscores that corticosteroid exposure can precipitate systemic dissemination even in patients with preserved CD4 counts. Although this condition carries a high risk of mortality, early recognition, targeted antibiotic therapy, and careful multidisciplinary management of underlying immunosuppression are critical to improving survival and minimizing neurological sequelae. Full article

Background/Objectives: SARS-CoV-2 infection has been linked to long-term neurological sequelae and structural brain alterations. Previous analyses, including baseline results from the COVIMMUNE-Clin study, showed brain volume reductions in COVID-19 patients. Longitudinal data on progression are scarce. This study examined brain volume changes 12 months after baseline MRI in individuals who have recovered from mild or severe COVID-19 compared with controls. Methods: In this IRB-approved cohort study, 112 out of 172 recruited age- and sex-matched participants (38 controls, 36 mild/asymptomatic 38 severe COVID-19) underwent standardized brain MRI 12 months after baseline. Volumetric analysis was performed using AI-based software (mdbrain). Regional volumes were compared between groups with respect to absolute and normalized values. Multivariate regression controlled for demographics. Results: After 12 months, a significant decline in right hippocampal volume was observed across all groups, most pronounced in severe COVID-19 (SEV: Δ = −0.32 mL, p = 0.001). Normalized to intracranial volume, the reduction remained significant (SEV: Δ = −0.0003, p = 0.001; ASY: Δ = −0.0001, p = 0.001; CTL: minimal reduction, Δ ≈ 0, p = 0.005). Minor reductions in frontal and parietal lobes (e.g., right frontal SEV: Δ = −1.35 mL, p = 0.001), largely fell within physiological norms. These mild regional changes are consistent with expected ageing-related variability and do not suggest pathological progression. No widespread progressive atrophy was detected. Conclusions: This study demonstrates delayed, severity-dependent right hippocampal atrophy in recovered COVID-19 patients, suggesting long-term vulnerability of this memory-related region. In contrast, no progression of atrophy in other areas was observed. These findings highlight the need for extended post-COVID neurological monitoring, particularly of hippocampal integrity and its cognitive relevance. Full article

Insomnia and depression are severe sequelae of COVID-19 and often occur simultaneously. Our study examined associations of insomnia and/or depression with cognitive impairments, white matter changes, and serum biomarkers. In total, 76 long COVID patients and 22 healthy controls were examined using neuropsychiatric (ISI, HADS, and HDRS) and cognitive (MoCA, Stroop, WMT, and TMT) tests, with their blood biomarkers (anti-SARS-CoV-2, BDNF, anti-S100, anti-MBP, and anti-PLP) investigated, and underwent MRI using macromolecular proton fraction (MPF) mapping to quantify myelination. The Insomnia (n = 14), Depression (n = 12), InsDep (comorbid insomnia–depression, n = 13), and PostCovid (long COVID without depression and insomnia, n = 32) groups were identified based on psychiatric/neurological diagnoses and neuropsychiatric assessment. Cognitive performance was most affected in the Insomnia group in the MoCA and CW Stroop tests. The Depression group underperformed in the TMT and W Stroop task; the InsDep group underperformed in the WMT. The Insomnia group showed the greatest demyelination, affecting commissural (CC and tapetum), projection (CR, IC, CST, cerebral peduncles, CP, and ML), and some association pathways (SLF, SFOF), as well as most juxtacortical regions, the thalamus, and the midbrain; these changes correlated with insomnia severity. The Depression and InsDep groups showed smaller but significant overall demyelination correlated with depression severity. The Depression group exhibited the highest MPF decrease in the globus pallidus, putamen, and external capsule, while the InsDep group demonstrated the highest demyelination of the association pathways IFOF, UF, and cingulum. The anti-PLP levels were the highest in the Insomnia group and correlated with both the persistence of insomnia/depression symptoms and demyelination. Demyelination in long COVID is associated with high levels of myelin-specific autoantibodies, but symptoms of insomnia and/or depression are associated with demyelination of a different set of brain structures. Full article

The COVID-19 pandemic has demonstrated that its effects go far beyond the initial respiratory illness, with many survivors experiencing lasting neurological problems. Some patients develop a condition known as Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), which includes current issues such as reduced cognitive function, chronic headaches, depression, neuropathic pain, and sensory disturbances. These symptoms can severely disrupt daily life and overall well-being. In this narrative review, we provide an overview of current understanding regarding the neurological effects of COVID-19, with a focus on Long COVID. We discuss possible underlying mechanisms, including direct viral invasion of the nervous system, immune-related damage, and vascular complications. We also summarize findings from cohort studies and meta-analyses that explore the causes, symptom patterns, and frequency of these neurological issues. Approximately one-third of people who have had COVID-19 report neurological symptoms, especially those who experienced severe illness or were infected with pre-Omicron variants. Emerging research has identified potential biomarkers such as neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) that may help in diagnosis. Treatment approaches under investigation include antiviral medications, nutraceuticals, and comprehensive rehabilitation programs. Factors like older age, existing health conditions, and genetic differences in ACE2 and TMPRSS2 genes may affect an individual’s risk. To effectively address these challenges, current research is essential to improve diagnostic methods, develop targeted treatments, and enhance rehabilitation strategies. Ultimately, a coordinated, multidisciplinary effort is crucial to reduce the neurological impact of Long COVID and support better recovery for patients. Full article

Background: COVID-19 has been associated with neurological and psychiatric manifestations, both at disease onset and during post-infectious sequelae, such as anxiety, depression, and sleep disturbances. Previous pandemics suggest potential for long-term neuropsychiatric consequences. Materials and Methods: We conducted a prospective longitudinal study in patients hospitalized with non-critical COVID-19, evaluating symptoms using validated psychometric instruments at discharge and after 3–6 and 12 months post-infection. Additionally, a four-year follow-up was performed through telephone interviews to document newly diagnosed psychiatric disorders and mortality. Results: At baseline, 22% of patients reported anxiety, 8% depression, and 16% poor sleep. Most symptoms improved within the first year, particularly during the first 3–6 months. At four-year follow-up, mortality reached 5%, while clinician-diagnosed psychiatric disorders increased to 6% for anxiety, 11% for depression, and 3% for mixed disorders. Anxiety and poor sleep—but not depression—were associated with the severity of the acute episode. Conclusions: Overall, post-COVID-19 anxiety, depression, and sleep disturbances were more prevalent than in the general population, though the rates were lower than those reported in other studies. Most symptoms resolved within the first year. However, new-onset cases of depression and other psychiatric disorders emerged during long-term follow-up, suggesting distinct trajectories of post-COVID-19 psychiatric morbidity. Full article

Bupropion overdose can result in severe neurological and cardiovascular toxicity. We describe a 16-year-old girl who ingested 4.2 g of extended-release bupropion (90.3 mg/kg), presenting with seizures and out-of-hospital cardiac arrest. After 21 min of cardiopulmonary resuscitation, she was resuscitated and admitted with profound metabolic acidosis and electrocardiographic abnormalities. Serum testing confirmed markedly elevated bupropion levels. During hospitalization, she developed delayed rhabdomyolysis, hypoxic encephalopathy, and persistent neurological sequelae, including Parkinsonism and cognitive deficits. Supportive care led to gradual recovery, with normalization of cardiac conduction and drug clearance by day 20, though residual deficits remained at discharge after seven weeks. This case highlights the life-threatening complications of bupropion toxicity, the delayed risk of seizures, and the need for vigilance for secondary complications such as rhabdomyolysis. Full article

Background and Clinical Significance: Abusive head trauma (AHT), formerly known as Shaken Baby Syndrome (SBS), is a major cause of morbidity and mortality in infants and young children. While the forensic aspects of acute AHT are well described, autopsy findings in long-term survivors who die later in life remain poorly documented. Case Presentation: We describe a male infant diagnosed with AHT at 2 months of age, who survived with severe neurological sequelae until 19 years. He developed tetraparesis and epileptic encephalopathy, and ultimately died during hospitalization for bilateral pneumonia. Forensic autopsy revealed bilateral acute exudative pneumonia with respiratory failure. Neuropathological examination documented extensive chronic encephalomalacia, gliosis, and microcalcifications consistent with longstanding sequelae of AHT. These findings supported a causal nexus between the abusive head trauma sustained in infancy and the fatal pulmonary complication in adolescence. Conclusions: This case highlights the importance of forensic autopsy in long-term survivors of AHT. Establishing the causal relationship between early abusive injuries and late mortality is essential for both medical understanding and medicolegal evaluation. Full article