Sensibilidad química múltiple en una niña de 8 años. Seguimiento durante 6 años / Multiple chemical sensitivity in an 8-year-old girl. A 6-year follow-up

La sensibilidad química múltiple (SQM) es una entidad escasamente comprendida y controvertida. La SQM es un síndrome polisintomático y multisistémico. Los sujetos con SQM muestran una sintomatología compleja debido a la intolerancia a los agentes químicos. Los síntomas incluyen malestar general, inestabilidad cardiovascular, irritación de órganos de los sentidos, desórdenes respiratorios, con hipersensibilidad que afecta a piel, recubrimiento epitelial de intestino, garganta y pulmones. Se presenta un caso de una mujer de 8 años, valorada por sensibilización química con síntomas inhalatorios y faríngeos, conjuntivitis, disfonía y accesos de tos con sensación de dificultad respiratoria. El seguimiento se ha realizado durante 6 años, durante los cuales se ha repetido el test inhalatorio en dos ocasiones con los mismos resultados concluyentes para el diagnóstico de SQM. El caso comunicado reúne los criterios de SQM, siendo excepcional el inicio de los síntomas a una edad tan temprana. (AU)

Multiple chemical sensitivity (MCS) is a controversial little understood entity. MCS is a multisystem and poly-symptomatic syndrome. MCS subjects display a complex symptomatology due to the intolerance of chemical agents. Symptoms include general discomfort, cardiovascular instability, sensory organs irritation, breath disorders, hypersensitivity affecting the skin and epithelial lining of the gut, throat and lungs. We report the case of an 8 years old female, assessed in medical consultation for chemical sensitization when presenting inhalation and pharyngeal symptoms, conjunctivitis, dysphonia, coughing spells and respiratory distress. A 6-year follow-up was carried out and the provocation inhaler test which was performed twice among that period obtained the same conclusive results for the diagnosis of MCS. The case submitted meets the criterion of MCS, being exceptional a debut of the symptons at such an early age. (AU)

Anosmia predicts memory impairment in post-COVID-19 syndrome: results of a neuropsychological cohort study.

Recovered COVID-19 patients frequently suffer of cognitive disorders. Several etiopathogenetic mechanisms have been considered for the brain complications in COVID-19 but results are uncertain. Amongst them, an olfactory route to SARS-CoV-2 brain infection might explain cognitive and memory disturbances in post-COVID-19 patients, given the cooccurrence of anosmia and possible underlying limbic involvement. The aims of the study are to investigate cognition of patients with post-COVID-19 syndrome, and to find clinical factors predicting cognitive and memory impairments. 18 patients with post-COVID-19 syndrome underwent neuropsychological assessment and evaluation of clinical parameters. Stepwise regression analysis was used between clinical parameters as factors and cognitive global scores as dependent variables. Since only anosmia predicted memory performances, repeated measures ANOVA of memory scores was conducted between anosmic and non-anosmic patients. We found lack of association between clinical parameters and cognitive performances. Only anosmia was a good predictor for memory performances, with anosmic subjects showing a temporo-mesial amnesic profile. Our study shows novel findings of causal association between transient anosmia during COVID-19 and memory disorders with temporo-mesial dysfunction, probably sharing a common pathophysiological mechanism, and suggesting a possible SARS-CoV 2 infection of the limbic brain via the olfactory route. In contrast to previous studies, cognitive dysfunctions were not associated with respiratory distress, comorbidity, and depression.

Drug delivery to the brain via the nasal route of administration: exploration of key targets and major consideration factors.

Background: Cranial nerve-related diseases such as brain tumors, Alzheimer's disease, and epilepsy are serious diseases that continue to threaten human. Brain-related diseases are increasing worldwide, including in the United States and Korea, and these increases are closely related to the exposure to harmful substances and excessive stress caused by rapid industrialization and environmental pollution. Drug delivery to the brain is very important for the effective prevention and treatment of brain-related diseases. However, due to the presence of the blood-brain barrier and the extensive first-pass metabolism effect, the general routes of administration such as oral and intravenous routes have limitations in drug delivery to the brain. Therefore, as an alternative, the nasal-brain drug delivery route is attracting attention as a route for effective drug delivery to the brain. Areas covered: This review includes physiological factors, advantages, limitations, current application status, especially in clinical applications, and the necessary factors for consideration in formulation development related to nasal-brain drug delivery. Expert opinion: The nasal-brain drug delivery route has the advantage of enhancing drug delivery to the brain locally, mainly through the olfactory route rather than the systemic circulation. The nasal-brain lymphatic system has recently attracted attention, and it has been implied that the delivery of anticancer drugs to the brain nervous system is possible effectively. However, there are limitations such as low drug permeability, as well as nasal mucosa and the mucociliary system, as obstacles in nasal-brain drug delivery. Therefore, to overcome the limitations of nasal-brain drug delivery, the use of nanocarriers and mucoadhesive agents is being attempted. However, very few drugs have been officially approved for clinical application via the nasal-brain drug delivery route. This is probably because the understanding of and related studies on nasal-brain drug delivery are limited. In this review, we tried to explore the major considerations and target factors in drug delivery through the nasal-brain route based on physiological knowledge and formulation research information. This will help to provide a mechanistic understanding of drug delivery through the nasal-brain route and bring us one step closer to developing effective formulations and drugs in consideration of the key factors for nasal-brain drug delivery.

Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: How?

Without protective and/or therapeutic agents the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection known as coronavirus disease 2019 is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS-CoV-2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS-CoV-2 components could use to reach the CNS and PNS, utilizing the within-body cross talk between organs. The majority of SARS-CoV-2-infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune-mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood-endothelial barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

Superparamagnetic Iron Oxide-Loaded Lipid Nanocarriers Incorporated in Thermosensitive In Situ Gel for Magnetic Brain Targeting of Clonazepam.

The objective of the study was to target clonazepam to the brain through the intranasal olfactory mucosa using nanolipid carriers loaded with superparamagnetic iron oxide nanoparticles (SPIONs) to allow nanocarrier guidance and retention with an external magnetic field. For improved delivery, the nanolipid carriers were incorporated in a thermosensitive mucoadhesive in situ gel. Different nanolipid carriers including solid lipid nanoparticles and nanostructured lipid carriers (NLC) were prepared and characterized with respect to particle size, zeta potential, entrapment efficiency, and in vitro release. The NLC composed of 3 solid lipids (Compritol® 888, stearic acid, and glyceryl monostearate) and 2 liquid oils (oleic acid and glyceryl monooleate) showed the most satisfactory characteristics and was loaded with SPION (NLC/SPION). Both formulae (NLC and NLC/SPION) were incorporated in an optimized thermosensitive mucoadhesive in situ system composed of 15% pluronic 127 and 0.75% sodium alginate and evaluated for the anticonvulsant action in chemically induced convulsive Swiss Albino mice. The treatment of animals with NLC/SPION significantly prolonged the onset times for convulsion and considerably protected the animals from death. One can thus hope for the emergence of a new intranasal treatment of epilepsy with consequent decrease in peripheral side effects of clonazepam.

Evidence for influenza virus CNS invasion along the olfactory route in an immunocompromised infant.

Central nervous system (CNS) disease is the most common extrarespiratory complication of influenza in humans. However, the pathogenesis, including the route of virus entry, is largely unknown. Here we present, for the first time, evidence of influenza virus entry into the CNS via the olfactory route in an immune-compromised infant. Since the nasal cavity is a primary site of influenza virus replication and is directly connected to the CNS via the olfactory nerve, these results imply that influenza virus invasion of the CNS may occur more often than previously believed.