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Frontiers in Pharmacology 2024Kaixinsan (KXS) is a noteworthy classical prescription, which consists of four Chinese medicinal herbs, namely Polygalae Radix, Ginseng Radix et Rhizoma, Poria, and... (Review)
Review
Kaixinsan (KXS) is a noteworthy classical prescription, which consists of four Chinese medicinal herbs, namely Polygalae Radix, Ginseng Radix et Rhizoma, Poria, and Acori Tatarinowii Rhizoma. KXS was initially documented in the Chinese ancient book Beiji Qianjin Yaofang written by Sun Simiao of the Tang Dynasty in 652 A.D. As a traditional Chinese medicine (TCM) prescription, it functions to nourish the heart and replenish Qi, calm the heart tranquilize the mind, and excrete dampness. Originally used to treat amnesia, it is now also effective in memory decline and applied to depression. Although there remains an abundance of literature investigating KXS from multiple aspects, few reviews summarize the features and research, which impedes better exploration and exploitation of KXS. This article intends to comprehensively analyze and summarize up-to-date information concerning the chemical constituents, pharmacology, pharmacokinetics, clinical applications, and safety of KXS based on the scientific literature, as well as to examine possible scientific gaps in current research and tackle issues in the next step. The chemical constituents of KXS primarily consist of saponins, xanthones, oligosaccharide esters, triterpenoids, volatile oils, and flavonoids. Of these, saponins are the predominant active ingredients, and increasing evidence has indicated that they exert therapeutic properties against mental disease. Pharmacokinetic research has illustrated that the crucial exposed substances in rat plasma after KXS administration are ginsenoside Re (GRe), ginsenoside Rb1 (GRb1), and polygalaxanthone III (POL). This article provides additional descriptions of the safety. In this review, current issues are highlighted to guide further comprehensive research of KXS and other classical prescriptions.
PubMed: 38362144
DOI: 10.3389/fphar.2024.1338024 -
CNS Drugs Feb 2024Patients with epilepsy may experience seizure clusters, which are described by the US Food and Drug Administration (FDA) as intermittent, stereotypic episodes of... (Review)
Review
Patients with epilepsy may experience seizure clusters, which are described by the US Food and Drug Administration (FDA) as intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient's usual seizure pattern. Untreated seizure clusters may increase the risk for status epilepticus, as well as decrease quality of life and increase burden on patients and care partners. Benzodiazepine therapies are the mainstay for acute treatment of seizure clusters and are often administered by nonmedical care partners outside a healthcare facility. Three rescue therapies are currently FDA-approved for this indication, with diazepam rectal gel being the first in 1997, for patients aged ≥ 2 years. Limitations of rectal administration (e.g., positioning and disrobing the patient, which may affect ease of use and social acceptability; interpatient variation in bioavailability) led to the investigation of the potential for nasal administration as an alternative. Midazolam nasal spray (MDS) was approved by the FDA in 2019 for patients aged ≥ 12 years and diazepam nasal spray (DNS) in 2020 for patients aged ≥ 6 years; these two intranasal therapies have differences in their formulations [e.g., organic solvents (MDS) vs. Intravail and vitamin E for absorption and solubility (DNS)], effectiveness (e.g., proportion of seizure clusters requiring only one dose), and safety profiles. In clinical studies, the proportion of seizure clusters for which only one dose of medication was used varied between the three approved rescue therapies with the highest single-dose rate for any time period for DNS; however, although studies for all three preparations enrolled patients with highly intractable epilepsy, inclusion and exclusion criteria varied, so the three cannot be directly compared. Treatments that have been used off-label for seizure clusters in the USA include midazolam for injection as an intranasal spray (indicated for sedation/anxiolysis/amnesia and anesthesia) and tablet forms of clonazepam (indicated for treatment for seizure disorders) and lorazepam (indicated for anxiety). In the European Union, buccal and intranasal midazolam are used for treating the indication of prolonged, acute convulsive seizures and rectal diazepam solution for the indication of epileptic and febrile convulsions; duration of effectiveness for these medications for the treatment of seizure clusters has not been established. This paper examines the literature context for understanding seizure clusters and their treatment and provides effectiveness, safety, and administration details for the three FDA-approved rescue therapies. Additionally, other medications that are used for rescue therapy in the USA and globally are discussed. Finally, the potential benefits of seizure action plans and candidates for their use are addressed. This paper is intended to provide details about the unique characteristics of rescue therapies for seizure clusters to help clarify appropriate treatment for individual patients.
Topics: Humans; Benzodiazepines; Midazolam; Anticonvulsants; Nasal Sprays; Quality of Life; Diazepam; Status Epilepticus; Epilepsy; Epilepsy, Generalized; Administration, Intranasal
PubMed: 38358613
DOI: 10.1007/s40263-023-01060-1 -
BMJ Open Feb 2024Hospital-based clinical decision tools support clinician decision-making when a child presents to the emergency department with a head injury, particularly regarding CT...
Which elements of hospital-based clinical decision support tools for the assessment and management of children with head injury can be adapted for use by paramedics in prehospital care? A systematic mapping review and narrative synthesis.
OBJECTIVE
Hospital-based clinical decision tools support clinician decision-making when a child presents to the emergency department with a head injury, particularly regarding CT scanning. However, there is no decision tool to support prehospital clinicians in deciding which head-injured children can safely remain at scene. This study aims to identify clinical decision tools, or constituent elements, which may be adapted for use in prehospital care.
DESIGN
Systematic mapping review and narrative synthesis.
DATA SOURCES
Searches were conducted using MEDLINE, EMBASE, PsycINFO, CINAHL and AMED.
ELIGIBILITY CRITERIA
Quantitative, qualitative, mixed-methods or systematic review research that included a clinical decision support tool for assessing and managing children with head injury.
DATA EXTRACTION AND SYNTHESIS
We systematically identified all in-hospital clinical decision support tools and extracted from these the clinical criteria used in decision-making. We complemented this with a narrative synthesis.
RESULTS
Following de-duplication, 887 articles were identified. After screening titles and abstracts, 710 articles were excluded, leaving 177 full-text articles. Of these, 95 were excluded, yielding 82 studies. A further 14 studies were identified in the literature after cross-checking, totalling 96 analysed studies. 25 relevant in-hospital clinical decision tools were identified, encompassing 67 different clinical criteria, which were grouped into 18 categories.
CONCLUSION
Factors that should be considered for use in a clinical decision tool designed to support paramedics in the assessment and management of children with head injury are: signs of skull fracture; a large, boggy or non-frontal scalp haematoma neurological deficit; Glasgow Coma Score less than 15; prolonged or worsening headache; prolonged loss of consciousness; post-traumatic seizure; amnesia in older children; non-accidental injury; drug or alcohol use; and less than 1 year old. Clinical criteria that require further investigation include mechanism of injury, clotting impairment/anticoagulation, vertigo, length of time of unconsciousness and number of vomits.
Topics: Child; Humans; Infant; Paramedics; Decision Support Systems, Clinical; Craniocerebral Trauma; Hospitals; Emergency Medical Services
PubMed: 38355171
DOI: 10.1136/bmjopen-2023-078363 -
European Journal of Case Reports in... 2024Transient myoclonic (TM) state in older adults is a neurological condition characterised by short-lived, repetitive myoclonus without consciousness disturbance. First...
BACKGROUND
Transient myoclonic (TM) state in older adults is a neurological condition characterised by short-lived, repetitive myoclonus without consciousness disturbance. First reported in 1992, it predominantly affects older individuals with chronic diseases. Despite its clear symptomatology, TM often remains under-recognised, leading to potential misdiagnoses.
CASE DESCRIPTION
We report a case of a 68-year-old woman with a history of chronic heart failure who developed TM during hospitalisation following medication adjustment for acute heart failure. The patient, who had no history of intracranial disease or epilepsy, experienced acute involuntary movements of the face and limbs three days after diuretic adjustment. She responded well to intravenous diazepam and oral clonazepam, with no recurrence of symptoms post-treatment.
DISCUSSION
TM presents with bilateral, irregular, and repetitive myoclonus, mostly affecting the head, neck and upper extremities. Diagnosis is clinical, based on symptomatology and normal laboratory results. This case underscores the importance of recognising TM in differential diagnosis, especially in older patients in the acute or recovery phase of infection, or with medication changes. The potential role of fluid volume changes in TM pathophysiology in patients with underlying conditions such as hypertension or chronic heart failure is also highlighted. This case emphasises the need for heightened awareness and knowledge of TM among healthcare professionals.
CONCLUSIONS
TM, though rare, requires awareness among clinicians for accurate diagnosis and management. It is crucial to avoid misdiagnosis and unnecessary interventions, and to provide appropriate information during care transitions, particularly in older adults with chronic conditions.
LEARNING POINTS
Transient myoclonic (TM) state is a rare neurological condition in older adults, characterised by brief and repetitive myoclonus, primarily affecting the head, neck and upper extremities.The distinctive clinical diagnostic feature is myoclonus occurring without disturbances in consciousness, without amnesia or paralysis, while retaining the ability to perform directed movements. This condition can manifest at rest, may worsen with posture or movement, and tends to improve during sleep.Management strategies include ensuring smooth care transitions, avoiding misdiagnosis and educating patients and families about the risk of recurrence.
PubMed: 38352808
DOI: 10.12890/2024_004254 -
Pathogens & Immunity 2023Lymphopenia is common in COVID-19. This has raised concerns that COVID-19 could affect the immune system akin to measles infection, which causes immune amnesia and a...
BACKGROUND
Lymphopenia is common in COVID-19. This has raised concerns that COVID-19 could affect the immune system akin to measles infection, which causes immune amnesia and a reduction in protective antibodies.
METHODS
We recruited COVID-19 patients (n = 59) in Helsinki, Finland, and collected plasma samples on 2 to 3 occasions during and after infection. We measured IgG antibodies to diphtheria toxin, tetanus toxoid, and pertussis toxin, along with total IgG, SARS-CoV-2 spike protein IgG, and neutralizing antibodies. We also surveyed the participants for up to 17 months for long-term impaired olfaction as a proxy for prolonged post-acute COVID-19 symptoms.
RESULTS
No significant differences were found in the unrelated vaccine responses while the serological response against COVID-19 was appropriate. During the acute phase of the disease, the SARSCoV-2 IgG levels were lower in outpatients when compared to inpatients. SARS-CoV-2 serology kinetics matched expectations. In the acute phase, anti-tetanus and anti-diphtheria IgG levels were lower in patients with prolonged impaired olfaction during follow up than in those without.
CONCLUSIONS
We could not detect significant decline in overall humoral immunity during or after COVID-19 infection. In severe COVID-19, there appears to be a temporary decline in total IgG levels.
PubMed: 38347963
DOI: 10.20411/pai.v8i2.627 -
Molecules (Basel, Switzerland) Jan 2024The role of endothelial nitric oxide synthase (eNOS) in the regulation of a variety of biological processes is well established, and its dysfunction contributes to brain...
The Impact of LY487379 or CDPPB on eNOS Expression in the Mouse Brain and the Effect of Joint Administration of Compounds with NO Releasers on MK-801- or Scopolamine-Driven Cognitive Dysfunction in Mice.
The role of endothelial nitric oxide synthase (eNOS) in the regulation of a variety of biological processes is well established, and its dysfunction contributes to brain pathologies, including schizophrenia or Alzheimer's disease (AD). Positive allosteric modulators (PAMs) of metabotropic glutamate (mGlu) receptors were shown to be effective procognitive compounds, but little is known about their impact on eNOS expression and stability. Here, we investigated the influence of the acute and chronic administration of LY487379 or CDPPB (mGlu2 and mGlu5 PAMs), on eNOS expression in the mouse brain and the effect of the joint administration of the ligands with nitric oxide (NO) releasers, spermineNONOate or DETANONOate, in different combinations of doses, on MK-801- or scopolamine-induced amnesia in the novel object recognition (NOR) test. Our results indicate that both compounds provoked eNOS monomer formation, and CDPPB at a dose of 5 mg/kg exaggerated the effect of MK-801 or scopolamine. The coadministration of spermineNONOate or DETANONOate enhanced the antiamnesic effect of CDPPB or LY487379. The best activity was observed for ineffective or moderate dose combinations. The results indicate that treatment with mGluR2 and mGluR5 PAMs may be burdened with the risk of promoting eNOS uncoupling through the induction of dimer dissociation. Administration of the lowest possible doses of the compounds with NO donors, which themselves have procognitive efficacy, may be proposed for the treatment of schizophrenia or AD.
Topics: Mice; Animals; Dizocilpine Maleate; Nitric Oxide; Scopolamine; Nitric Oxide Synthase Type III; Cognitive Dysfunction; Brain; Allosteric Regulation; Nitroso Compounds; Pyrazoles; Benzamides; Sulfonamides; Pyridines
PubMed: 38338372
DOI: 10.3390/molecules29030627 -
Frontiers in Neurology 2024Acute amnestic syndrome is an uncommon clinical presentation of neurological disease. Differential diagnosis encompasses several syndromes including Wernicke-Korsakoff...
INTRODUCTION
Acute amnestic syndrome is an uncommon clinical presentation of neurological disease. Differential diagnosis encompasses several syndromes including Wernicke-Korsakoff and transient global amnesia (TGA). Structural lesions of the fornix account for a minority of cases of acute amnestic syndromes. Etiology varies from iatrogenic injury to ischemic, inflammatory, or neoplastic lesions. A prompt diagnosis of the underlying pathology is essential but challenging. The aim of this review is to systematically review the existing literature regarding cases of acute amnestic syndrome associated with non-iatrogenic lesions of the fornix.
METHODS
We performed a systematic literature search on PubMed, Scopus, and Web of Science up to September 2023 to identify case reports and case series of patients with amnestic syndrome due to fornix lesions. The systematic review was conducted according to PRISMA guidelines. The research was limited to articles written in English. Cases of fornix damage directly ascribable to a surgical procedure were excluded.
RESULTS
A total of 52 publications reporting 55 cases were included in the review. Focusing on acute/subacute onset, vascular etiology was highly prevalent, being responsible for 78% of cases, 40/55 (74%) of which were due to acute ischemic stroke. The amnestic syndrome was characterized by anterograde amnesia in all patients, associated with retrograde amnesia in 27% of cases. Amnesia was an isolated presentation in most cases. Up to two thirds of patients had persistent memory deficits of any severity at follow-up.
DISCUSSION
Acute amnestic syndrome can be rarely caused by fornix lesions. In most cases of acute/subacute presentation, the etiology is ischemic stroke, mainly caused by strokes involving the subcallosal artery territory. The differential diagnosis is challenging and a distinction from common mimics is often difficult on a clinical basis. A high index of suspicion should be maintained to avoid misdiagnosis and provide adequate acute treatment to patients with time-dependent disease, also employing advanced neuroimaging. More research is needed to better understand the outcome and identify prognostic factors in patients with amnestic syndrome due to fornix lesions.
PubMed: 38333604
DOI: 10.3389/fneur.2024.1338291 -
Annals of Medicine and Surgery (2012) Feb 2024Limbic encephalitides (LE) have symptoms and signs of new-onset seizures accompanied by cognitive impairment and signal changes in the MRI of the limbic system in the...
INTRODUCTION AND IMPORTANCE
Limbic encephalitides (LE) have symptoms and signs of new-onset seizures accompanied by cognitive impairment and signal changes in the MRI of the limbic system in the brain. Numerous antibodies against the neurons and synapses have been detected so far. Of those, antiglutamic acid decarboxylase antibody (Anti-GAD Ab) impairs the gamma amino butyric acid, one of the primary mediators that naturally prevents abnormal neuronal activity causing seizure.
CASE PRESENTATION
The authors have reported a case of anti-GAD Ab LE in a diabetic male adolescent who responded dramatically to intravenous immunoglobulin and reviewed all similar pediatric cases for 15 years now.
CLINICAL DISCUSSION
The symptoms in children suffering from anti-GAD LE in three categories, systemic, psychiatric, and neurological, are heterogeneous. The most common manifestations were seizures followed by altered mental status and behavioral changes, respectively. The two main clinical scenarios described in GAD65-mediated autoimmune epilepsy are (1) an acute/subacute onset of seizures alone or seizures (including new-onset refractory status epilepticus, NORSE) accompanied by some degrees of cognitive and psychiatric manifestations, including amnesia and mesiotemporal inflammatory involvement consistent with LE and (2) epilepsy without clinical or MRI evidence of active central nervous system inflammation.
CONCLUSION
Although rare, the neurologist should consider the potential role of anti-GAD ab-associated encephalitis in the presence of diabetes mellitus.
PubMed: 38333287
DOI: 10.1097/MS9.0000000000001653 -
Nature Communications Feb 2024Measles cases have surged pre-COVID-19 and the pandemic has aggravated the problem. Most measles-associated morbidity and mortality arises from destruction of...
Measles cases have surged pre-COVID-19 and the pandemic has aggravated the problem. Most measles-associated morbidity and mortality arises from destruction of pre-existing immune memory by measles virus (MeV), a paramyxovirus of the morbillivirus genus. Therapeutic measles vaccination lacks efficacy, but little is known about preserving immune memory through antivirals and the effect of respiratory disease history on measles severity. We use a canine distemper virus (CDV)-ferret model as surrogate for measles and employ an orally efficacious paramyxovirus polymerase inhibitor to address these questions. A receptor tropism-intact recombinant CDV with low lethality reveals an 8-day advantage of antiviral treatment versus therapeutic vaccination in maintaining immune memory. Infection of female ferrets with influenza A virus (IAV) A/CA/07/2009 (H1N1) or respiratory syncytial virus (RSV) four weeks pre-CDV causes fatal hemorrhagic pneumonia with lung onslaught by commensal bacteria. RNAseq identifies CDV-induced overexpression of trefoil factor (TFF) peptides in the respiratory tract, which is absent in animals pre-infected with IAV. Severe outcomes of consecutive IAV/CDV infections are mitigated by oral antivirals even when initiated late. These findings validate the morbillivirus immune amnesia hypothesis, define measles treatment paradigms, and identify priming of the TFF axis through prior respiratory infections as risk factor for exacerbated morbillivirus disease.
Topics: Animals; Female; Ferrets; Influenza A Virus, H1N1 Subtype; Measles; Measles virus; Distemper Virus, Canine; Antiviral Agents
PubMed: 38331906
DOI: 10.1038/s41467-024-45418-5 -
Cureus Jan 2024Transient global amnesia (TGA) constitutes a rare clinical entity that manifests with temporary memory without any other neurological manifestation. Several pathogenetic...
Transient global amnesia (TGA) constitutes a rare clinical entity that manifests with temporary memory without any other neurological manifestation. Several pathogenetic mechanisms have been implicated, including temporal hypoperfusion, venous congestion, and cortical spreading potentials. Accordingly, the only relevant imaging findings are hippocampal CA1 areas of restricted diffusion on diffusion-weighted images. In the current case report, we present the rare case of a patient with TGA associated with bilateral petrous apex cephalocele (PAC). A 63-year-old female presented with a single episode of transient memory. The brain MRI showed a bilateral PAC and an empty sella. The patient was neurologically intact upon examination and was conservatively managed. There was no symptom recurrence during the six months of follow-up. We hypothesize that the presence of the meningocele could be associated with the pathogenesis of TGA. To the best of our knowledge, this is the first case of a petrous apex meningocele presenting with TGA. Most previously reported patients were females in their fourth decade of life, usually presenting with headaches or incidentally. Almost half of the cases were bilateral, with an empty sella. Surgical treatment was reserved for symptomatic patients with cerebrospinal fluid leaks and excruciating trigeminal neuralgia. Patients with TGA may be associated with temporal lesions, including PAC. Likewise, PAC is an extremely rare clinical entity that could occasionally present with TGA.
PubMed: 38322086
DOI: 10.7759/cureus.51778