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International Journal of Nanomedicine 2024Addressing disorders related to the central nervous system (CNS) remains a complex challenge because of the presence of the blood-brain barrier (BBB), which restricts...
Addressing disorders related to the central nervous system (CNS) remains a complex challenge because of the presence of the blood-brain barrier (BBB), which restricts the entry of external substances into the brain tissue. Consequently, finding ways to overcome the limited therapeutic effect imposed by the BBB has become a central goal in advancing delivery systems targeted to the brain. In this context, the intranasal route has emerged as a promising solution for delivering treatments directly from the nose to the brain through the olfactory and trigeminal nerve pathways and thus, bypassing the BBB. The use of lipid-based nanoparticles, including nano/microemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, has shown promise in enhancing the efficiency of nose-to-brain delivery. These nanoparticles facilitate drug absorption from the nasal membrane. Additionally, the in situ gel (ISG) system has gained attention owing to its ability to extend the retention time of administered formulations within the nasal cavity. When combined with lipid-based nanoparticles, the ISG system creates a synergistic effect, further enhancing the overall effectiveness of brain-targeted delivery strategies. This comprehensive review provides a thorough investigation of intranasal administration. It delves into the strengths and limitations of this specific delivery route by considering the anatomical complexities and influential factors that play a role during dosing. Furthermore, this study introduces strategic approaches for incorporating nanoparticles and ISG delivery within the framework of intranasal applications. Finally, the review provides recent information on approved products and the clinical trial status of products related to intranasal administration, along with the inclusion of quality-by-design-related insights.
Topics: Administration, Intranasal; Blood-Brain Barrier; Brain; Drug Delivery Systems; Lipids; Liposomes; Nanoparticles; Nasal Mucosa
PubMed: 38414526
DOI: 10.2147/IJN.S439181 -
International Journal of Infectious... Jan 2024Symptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but...
OBJECTIVES
Symptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but research on children is lacking. This study aimed to analyze the incidence of neurologic involvement in patients diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C); and also to summarize current literature on possible neuroimaging findings in SARS-CoV-2 infected children.
METHODS
A literature search in six electronic databases was performed to retrieve case series, cohort studies, and cross-sectional studies on neurologic involvement in COVID-19 patients younger than 21 years of age published between December 2019 to September 2023, including COVID-19 patients.
RESULTS
A total of 2224 patients with MIS-C from 10 cohorts and cross-sectional studies suggested that neurologic involvement in these subsets ranges from 8.5% to 32.1%. Symptoms included acute encephalitis, seizures, stroke, cranial nerve palsy, nausea/vomiting, and intracranial hypertension. Neuroradiology findings of 114 children from 50 case reports included splenial or acute disseminated encephalomyelitis (ADEM)-like lesions, cytotoxic brain edema, autoimmune demyelinating diseases, ischemic stroke and arteritis, venous thrombosis, intracranial hemorrhage, meningitis, posterior reversible encephalopathy syndrome, anti-N-methyl-D-aspartate receptor autoimmune encephalitis, acute hemorrhagic leukoencephalitis, hydrocephalus, olfactory bulb atrophy, cerebellitis, and acute necrotizing encephalitis.
CONCLUSION
Radiologic findings of SARS-CoV-2 infection in the pediatric population are diverse. Neuroimaging studies should be considered in critically ill patients to rule out neurologic involvement and facilitate early interventions.
Topics: Adult; Humans; Child; COVID-19; SARS-CoV-2; Cross-Sectional Studies; Posterior Leukoencephalopathy Syndrome; Neuroimaging; Systemic Inflammatory Response Syndrome
PubMed: 37944584
DOI: 10.1016/j.ijid.2023.11.006 -
Therapeutic Advances in Chronic Disease 2023Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of... (Review)
Review
BACKGROUND
Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking.
OBJECTIVE
This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review.
DESIGN
Systematic review of randomized controlled trials (RCTs).
METHODS
A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane 'risk of bias' tool. A qualitative analysis was conducted due to heterogeneity of included studies.
RESULTS
A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program.
CONCLUSION
CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.
PubMed: 37841213
DOI: 10.1177/20406223231204727 -
Neurosurgical Review Sep 2023Optic canal unroofing (OCU) has gradually become a routine technique for tuberculum sellae meningiomas (TSMs) resection. This meta-analysis aimed to evaluate the... (Meta-Analysis)
Meta-Analysis Review
Optic canal unroofing (OCU) has gradually become a routine technique for tuberculum sellae meningiomas (TSMs) resection. This meta-analysis aimed to evaluate the efficacy and safety of OCU. A systematic review and meta-analysis of the published literature on this topic from 2003 to 2023 were conducted in accordance with the PRISMA guidelines. Rigorous statistical analysis with a p-value was performed for related change in visual improvement, gross total resection (GTR), visual deterioration, and olfactory nerve damage. The study included 15 articles with 384 patients in whom OCU was performed by the transcranial approach (TCA) or the endoscopic endonasal approach (EEA). Of these, 341 patients had preoperative visual loss, and 266 patients had postoperative visual recovery. The overall rate of visual improvement was 0.803 (95% CI: 0.733-0.874, p < 0.01). The rate of visual improvement in the EEA and TCA groups was 0.884 (95% CI: 0.803-0.965, p < 0.01) and 0.788 (95% CI: 0.700-0.875, p < 0.01). Further analysis of classification shows that the rate of visual improvement in Type I: < 2 cm was 0.889(95% CI: 0.739-0.969), Type II:2-4 cm was 0.844(95% CI: 0.755-0.910), Type III: > 4 cm was 0.500(95% CI: 0.068-0.932) and the total was 0.853(95% CI: 0.779-0.927 p < 0.01) with low heterogeneity of I = 20.80%.Twelve studies separately reported GTR with OCU was 293; the rate of GTR was 0.911 (95% CI: 0.848-0.961, p < 0.01). And the rate of GTR in Type I: < 2 cm was 0.933(95% CI: 0.817-0.986), Type II:2-4 cm was 0.880(95% CI: 0.800-0.936), Type III: > 4 cm was 0.600(95% CI: 0.147-0.947). The total was 0.897(95% CI: 0.830-0.965 p < 0.01) with low heterogeneity of I = 34.57%. The related complications of OCU were visual deterioration and olfactory nerve damage. Visual decline was reported in nine studies, and the rate was 0.077 (95% CI: 0.041-0.113, p < 0.01). Six studies reported olfactory nerve damage, and the overall rate was 0.054 (95% CI: 0.019-0.090, p < 0.01). OCU could significantly recover preoperative impaired vision and make GTR easier to achieve, which was also a safe and effective technique in TSM.
Topics: Humans; Meningioma; Postoperative Period; Skull Base Neoplasms; Meningeal Neoplasms
PubMed: 37698750
DOI: 10.1007/s10143-023-02151-9 -
PloS One 2023There is increasing evidence of both central and peripheral nervous system (PNS) involvement in COVID-19. We conducted this systematic literature review to investigate...
There is increasing evidence of both central and peripheral nervous system (PNS) involvement in COVID-19. We conducted this systematic literature review to investigate the characteristics, management and outcomes of patients with PNS, including the types and severity of cranial nerves (CN) involvement. We systematically searched on PubMed for studies reporting adult patients diagnosed with COVID-19 and PNS involvement until July 2021. From 1670 records, 225 articles matched the inclusion criteria, with a total of 1320 neurological events, in 1004 patients. There were 805 (61%) CN, 350 (26.5%) PNS, and 165 (12.5%) PNS plus CN events. The most frequently involved CN were the facial, vestibulo-cochlear and olfactory nerve in 27.3%, 25.4% and 16.1%, respectively. Guillain-Barre syndrome spectrum was identified in 84.2% of PNS events. We analysed 328 patients reported in 225 articles with CN, PNS, and PNS plus CN involvement. The patients with CN involvement were younger (mean age 46.2±17.1, p = .003), and were more frequently treated as outpatients (p < .001), mostly with glucocorticoids (p < .001). Patients that had PNS with or without CN involvement were more likely to be hospitalized (p < .001), and to receive intravenous immunoglobulins (p = .002) or plasma exchange (p = .002). Patients with CN, PNS, and PNS plus CN had severe COVID -19 disease in 24.8%, 37.3%, 34.9% respectively. The most common neurological outcome was mild/moderate sequelae in patients with CN, PNS, and PNS plus CN in 54.7%, 67.5% and 67.8% respectively (p = .1) and no significant difference was found between the three categories regarding death, disease severity, time from disease onset to neurological symptoms, lack of improvement and complete recovery. CN involvement was the most frequent PNS finding. All three categories of PNS involvement were rather associated to non-severe COVID-19 but it may be an important cause of hospitalization and post COVID-19 sequelae.
Topics: Adult; Humans; Middle Aged; COVID-19; Guillain-Barre Syndrome; Immunoglobulins, Intravenous; Plasma Exchange; Peripheral Nervous System
PubMed: 37023030
DOI: 10.1371/journal.pone.0283827 -
Cureus Nov 2022The COVID-19 pandemic has created huge economic and healthcare burdens. In most cases, the virus affects the lungs and causes respiratory symptoms. Additionally, its... (Review)
Review
The COVID-19 pandemic has created huge economic and healthcare burdens. In most cases, the virus affects the lungs and causes respiratory symptoms. Additionally, its impact on the cranial nerves remains unclear. We thus aimed to investigate cranial nerve dysfunction in patients with COVID-19 infection. We conducted a systematic literature search of relevant and eligible literature in five databases: PubMed, Web of Science, Medline, EBSCO, and Google Scholar. Our sample included 21 case reports, one case series with 29 patients, and one analytical study with 135 cases. Participant ages ranged from 23 months to 72 years (mean age of 47.5 ± 19.02). The mean time from respiratory symptoms to the onset of neurological signs was (9.6 ± 7.4) days, and the mean recovery time was (16.3 ± 15.3) days. Cranial nerve impairment associated with COVID-19 infection has affected a large population, from infants to the elderly. Facial and abducent nerves were the most commonly affected cranial nerves with reported good prognosis or complete recovery within a few days to weeks. Olfactory dysfunctions were widely detected among COVID-19 patients.
PubMed: 36589199
DOI: 10.7759/cureus.31997 -
The Laryngoscope Jun 2022Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can potentially shed light on its pathogenesis, and guide clinicians in prognostication and intervention.
METHODS
PubMed, Embase, Cochrane, SCOPUS were searched from inception to August 1, 2021. Three reviewers selected observational studies, case series, and case reports reporting radiological changes in the olfactory structures, detected on magnetic resonance imaging, computed tomography, or other imaging modalities, in patients aged ≥18 years with COVID-19 infection and OD, following preferred reporting items for systematic reviews and meta-analyses guidelines and a PROSPERO-registered protocol (CRD42021275211). We described the proportion of radiological outcomes, and used random-effects meta-analyses to pool the prevalence of olfactory cleft opacification, olfactory bulb signal abnormalities, and olfactory mucosa abnormalities in patients with and without COVID-19-associated OD.
RESULTS
We included 7 case-control studies (N = 353), 11 case series (N = 154), and 12 case reports (N = 12). The pooled prevalence of olfactory cleft opacification in patients with COVID-19 infection and OD (63%, 95% CI = 0.38-0.82) was significantly higher than that in controls (4%, 95% CI = 0.01-0.13). Conversely, similar proportions of cases and controls demonstrated olfactory bulb signal abnormalities (88% and 94%) and olfactory mucosa abnormalities (2% and 0%). Descriptive analysis found that 55.6% and 43.5% of patients with COVID-19 infection and OD had morphological abnormalities of the olfactory bulb and olfactory nerve, respectively, while 60.0% had abnormal olfactory bulb volumes.
CONCLUSION
Our findings implicate a conductive mechanism of OD, localized to the olfactory cleft, in approximately half of the affected COVID-19 patients. Laryngoscope, 132:1260-1274, 2022.
Topics: Adolescent; Adult; COVID-19; Humans; Olfaction Disorders; Olfactory Bulb; Olfactory Mucosa; Smell
PubMed: 35318656
DOI: 10.1002/lary.30078 -
Chinese Medical Sciences Journal =... Mar 2022Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection. In anosmic patients, SARS-CoV-2 temporarily alters the signaling process in olfactory...
Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection. In anosmic patients, SARS-CoV-2 temporarily alters the signaling process in olfactory nerve cells and olfactory bulb (OB), which eventually damages the structure of the olfactory epithelium, leading to a permanent disorder in the olfactory pathway that this damaged structure is showed in MRI imaging Methods Two investigators independently searched four databases consisting of PubMed, ProQuest, Scopus, and Web of Science for relevant records as of November 11, 2020 with no time, space, and language restrictions. Google Scholar was also searched for the related resources within the time limit of 2020. All the found articles were reviewed based on the PRISMA flow diagram. Qualitative studies, case reports, editorials, letters, and other non-original studies were excluded from this systematic analysis. Results Initial search yielded 434 records. After reviewing the titles and abstracts, we selected 74 articles; finally, 8 articles were depicted to be investigated and read in full text. The obtained results showed an increase in the width and volume of the olfactory cleft (OC), complete or partial destruction of OC, and complete occlusion of OC in COVID-19 patients. Deformation and degeneration as well as a subtle asymmetry were evident in the OBs. Computed tomography (CT), meganetic resonance imaging (MRI), and positron emission tomography (PET) were used to detect the outcomes of anosmia in these studies. Conclusions The changes in OC are greater than those in OB in patients with COVID-19, mainly due to the inflammatory and immune responses in OC. However, fewer changes in OB are due to neurological or vascular disorders. Topical steroid therapy and topical saline can be helpful.
PubMed: 35256044
DOI: 10.24920/003982 -
European Journal of Neurology Oct 2021Mounting evidence supports an association between Guillain-Barré syndrome spectrum (GBSs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Mounting evidence supports an association between Guillain-Barré syndrome spectrum (GBSs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, GBSs in the setting of coronavirus disease 2019 (COVID-19) remains poorly characterized, whilst GBSs prevalence amongst COVID-19 patients has not been previously systematically evaluated using a meta-analytical approach.
METHODS
A systematic review and meta-analysis of observational cohort and case series studies reporting on the occurrence, clinical characteristics and outcomes of patients with COVID-19-associated GBSs was performed. A random-effects model was used to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), compared to non-COVID-19, contemporary or historical GBSs patients.
RESULTS
Eighteen eligible studies (11 cohorts, seven case series) were identified including a total of 136,746 COVID-19 patients. Amongst COVID-19 patients, including hospitalized and non-hospitalized cases, the pooled GBSs prevalence was 0.15‰ (95% CI 0%-0.49‰; I = 96%). Compared with non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds for demyelinating GBSs subtypes (OR 3.27, 95% CI 1.32%-8.09%; I = 0%). In SARS-CoV-2-infected patients, olfactory or concomitant cranial nerve involvement was noted in 41.4% (95% CI 3.5%-60.4%; I = 46%) and 42.8% (95% CI 32.8%-53%; I = 0%) of the patients, respectively. Clinical outcomes including in-hospital mortality were comparable between COVID-19 GBSs patients and non-infected contemporary or historical GBSs controls.
CONCLUSION
GBSs prevalence was estimated at 15 cases per 100,000 SARS-CoV-2 infections. COVID-19 appears to be associated with an increased likelihood of GBSs and with demyelinating GBSs variants in particular.
Topics: COVID-19; Guillain-Barre Syndrome; Hospital Mortality; Humans; Prevalence; SARS-CoV-2
PubMed: 33837630
DOI: 10.1111/ene.14860 -
Journal of Neurology Aug 2021To perform an updated review of the literature on the neurological manifestations of COVID-19-infected patients METHODS: A PRISMA-guideline-based systematic review was...
OBJECTIVE
To perform an updated review of the literature on the neurological manifestations of COVID-19-infected patients METHODS: A PRISMA-guideline-based systematic review was conducted on PubMed, EMBASE, and SCOPUS. Series reporting neurological manifestations of COVID-19 patients were studied.
RESULTS
39 studies and 68,361 laboratory-confirmed COVID-19 patients were included. Up to 21.3% of COVID-19 patients presented neurological symptoms. Headache (5.4%), skeletal muscle injury (5.1%), psychiatric disorders (4.6%), impaired consciousness (2.8%), gustatory/olfactory dysfunction (2.3%), acute cerebrovascular events (1.4%), and dizziness (1.3%), were the most frequently reported neurological manifestations. Ischemic stroke occurred among 1.3% of COVID-19 patients. Other less common neurological manifestations were cranial nerve impairment (0.6%), nerve root and plexus disorders (0.4%), epilepsy (0.7%), and hemorrhagic stroke (0.15%). Impaired consciousness and acute cerebrovascular events were reported in 14% and 4% of patients with a severe disease, respectively, and they were significantly higher compared to non-severe patients (p < 0.05). Individual patient data from 129 COVID-19 patients with acute ischemic stroke (AIS) were extracted: mean age was 64.4 (SD ± 6.2), 78.5% had anterior circulation occlusions, the mean NIHSS was 15 (SD ± 7), and the intra-hospital mortality rate was 22.8%. Admission to the intensive care unit (ICU) was required among 63% of patients.
CONCLUSION
This updated review of literature, shows that headache, skeletal muscle injury, psychiatric disorders, impaired consciousness, and gustatory/olfactory dysfunction were the most common neurological symptoms of COVID-19 patients. Impaired consciousness and acute cerebrovascular events were significantly higher among patients with a severe infection. AIS patients required ICU admission in 63% of cases, while intra-hospital mortality rate was close to 23%.
Topics: Brain Ischemia; COVID-19; Humans; Middle Aged; Nervous System Diseases; SARS-CoV-2; Stroke
PubMed: 33125542
DOI: 10.1007/s00415-020-10285-9