-
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 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2023A systematic review of literature on the issue of involvement in the sense of smell, as well as the interaction between the trigeminal and olfactory nerves, was carried...
A systematic review of literature on the issue of involvement in the sense of smell, as well as the interaction between the trigeminal and olfactory nerves, was carried out. The article discusses the features of the chemical perception systems, as well as the treatment of olfactory disorders using transcranial electrical stimulation of the trigeminal nerve.
Topics: Humans; Smell; Olfaction Disorders; Transcranial Direct Current Stimulation; Trigeminal Nerve
PubMed: 38147376
DOI: 10.17116/jnevro20231231217 -
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 -
Respiratory Physiology & Neurobiology May 2023The perception of breathlessness is mechanistically linked to the awareness of increased inspiratory neural drive (IND). Stimulation of upper airway cold receptors on... (Review)
Review
The perception of breathlessness is mechanistically linked to the awareness of increased inspiratory neural drive (IND). Stimulation of upper airway cold receptors on the trigeminal nerve (TGN) with TGN agonists such as menthol or cool air to the face/nose has been hypothesized to reduce breathlessness by decreasing IND. The aim of this systematic scoping review was to identify and summarize the results of studies in animals and humans reporting on the impact of TGN stimulation or blockade on measures of IND. Thirty-one studies were identified, including 19 in laboratory animals and 12 in human participants. Studies in laboratory animals consistently reported that as TGN activity increased, measures of IND decreased (e.g., phrenic nerve activity). In humans, stimulation of the TGN with a stream of cool air to the face/nose decreased the sensitivity of the ventilatory chemoreflex response to hypercapnia. Otherwise, TGN stimulation with menthol or cool air to the face/note had no effect on measures of IND in humans. This review provides new insight into a potential neural mechanism of breathlessness relief with selected TGN agonists.
Topics: Animals; Humans; Menthol; Olfactory Nerve; Dyspnea; Nose; Trigeminal Nerve
PubMed: 36792044
DOI: 10.1016/j.resp.2023.104035 -
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 -
Molecular Neurobiology Oct 2022Neural regeneration has troubled investigators worldwide in the past decades. Currently, cell transplantation emerged as a breakthrough targeted therapy for spinal cord... (Review)
Review
Neural regeneration has troubled investigators worldwide in the past decades. Currently, cell transplantation emerged as a breakthrough targeted therapy for spinal cord injury (SCI) in the neurotrauma field, which provides a promising strategy in neural regeneration. Olfactory ensheathing cells (OECs), a specialized type of glial cells, is considered as the excellent candidate due to its unique variable and intrinsic regeneration-supportive properties. In fact, OECs could support olfactory receptor neuron turnover and axonal extension, which is essential to maintain the function of olfactory nervous system. Hitherto, an increasing number of literatures demonstrate that transplantation of OECs exerts vital roles in neural regeneration and functional recovery after neural injury, including central and peripheral nervous system. It is common knowledge that the deteriorating microenvironment (ischemia, hypoxia, scar, acute and chronic inflammation, etc.) resulting from injured nervous system is adverse for neural regeneration. Interestingly, recent studies indicated that OECs could promote neural repair through improvement of the disastrous microenvironments, especially to the overwhelmed inflammatory responses. Although OECs possess unusual advantages over other cells for neural repair, particularly in SCI, the mechanisms of OEC-mediated neural repair are still controversial with regard to anti-inflammation. Therefore, it is significant to summarize the anti-inflammation property of OECs, which is helpful to understand the biological characteristics of OECs and drive future studies. Here, we mainly focus on the anti-inflammatory role of OECs to make systematic review and discuss OEC-based therapy for CNS injury.
Topics: Anti-Inflammatory Agents; Cell Transplantation; Humans; Nerve Regeneration; Neuroglia; Olfactory Bulb; Spinal Cord; Spinal Cord Injuries
PubMed: 35962300
DOI: 10.1007/s12035-022-02983-4 -
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