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International Journal of Molecular... Jul 2023Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various... (Review)
Review
Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various physiological and pathological processes in the brain, including water homeostasis, cell migration, and inflammation, among others. Epileptogenesis is a complex and multifactorial process that involves alterations in the structure and function of neuronal networks. Recent evidence suggests that AQPs may also play a role in the pathogenesis of epilepsy. In animal models of epilepsy, AQPs have been shown to be upregulated in regions of the brain that are involved in seizure generation, suggesting that they may contribute to the hyperexcitability of neuronal networks. Moreover, genetic studies have identified mutations in AQP genes associated with an increased risk of developing epilepsy. Our review aims to investigate the role of AQPs in epilepsy and seizure onset from a pathophysiological point of view, pointing out the potential molecular mechanism and their clinical implications.
Topics: Animals; Aquaporins; Water; Homeostasis; Brain; Seizures
PubMed: 37569297
DOI: 10.3390/ijms241511923 -
Nutrition Research (New York, N.Y.) May 2024The quality of a mother's diet is important to ensure child growth and development and keep women healthy. This systematic review aimed to identify the outcomes of a... (Review)
Review
The quality of a mother's diet is important to ensure child growth and development and keep women healthy. This systematic review aimed to identify the outcomes of a carbohydrate-restricted diet during lactation. PubMed, EMBASE, Scopus, Web of Science, and LILACS were searched for studies published between 2012 and 2023; 16 studies were selected, all of them case reports or care series. The carbohydrate restriction described in the papers mainly was ketogenic, low-carb, low-carbohydrate and high-fat, and modified ketogenic diets. The main goal of women undertaking these diets was weight loss, with therapeutic purposes (monitored and supervised by health professionals) in only 2 cases: (1) ketogenic diet therapy for treatment of seizures in the infant and (2) to reduce symptoms of mother's gastroesophageal reflux. Most articles reported that lactating women were hospitalized, experiencing symptoms such as vomiting, muscle weakness, nausea, abdominal pain, general malaise, and fatigue. However, articles did not mention poor outcomes for the infants. Most of the studies in this review were published in the past 3 years, indicating a possible increase in cases of women practicing carbohydrate restriction during lactation for weight loss caused by body dissatisfaction. In conclusion, carbohydrate restriction during lactation may be harmful to the lactating woman and contribute to the state of lactational ketoacidosis, but infant outcomes are mainly a change in feeding patterns. Thus, education on food and nutrition is necessary for this population.
Topics: Humans; Lactation; Female; Diet, Carbohydrate-Restricted; Diet, Ketogenic; Weight Loss; Dietary Carbohydrates; Breast Feeding; Adult; Ketosis; Infant; Maternal Nutritional Physiological Phenomena
PubMed: 38565002
DOI: 10.1016/j.nutres.2024.02.007 -
Journal of Neuro-oncology Sep 2023Primary brain neoplasms are the most common solid tumors in pediatric patients and seizures are a common presenting symptom. Surgical intervention improves oncologic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Primary brain neoplasms are the most common solid tumors in pediatric patients and seizures are a common presenting symptom. Surgical intervention improves oncologic outcomes and seizure burden. A better understanding of factors that influence seizure outcomes in the surgical management of primary brain tumors of childhood can guide treatment approach thereby improving patient quality of life.
METHODS
We performed a systematic analysis using articles queried from PubMed, EMBASE, and Cochrane published from January 1990 to August 2022 to determine predictors of seizure outcomes in pediatric patients undergoing resection of primary brain tumors.
RESULTS
We identified 24 retrospective cohort studies, one prospective cohort study, and one mixed retrospective and prospective study for the systematic analysis. A total of 831 pediatric patients were available for analysis. 668 (80.4%) patients achieved seizure freedom after surgery. Complete tumor resection increased the likelihood of a seizure-free (Engel I) outcome compared to subtotal resection (OR 7.1, 95% CI 2.3-21.9). Rates of Engel I seizure outcomes did not significantly differ based on factors such as age at seizure onset, duration of epilepsy, gender, tumor laterality, or age at surgery, but trended towards significance for improved outcomes in temporal lobe tumors.
CONCLUSION
Primary brain tumors in the pediatric population are commonly associated with seizures. Resection of these lesions reduces seizure burden and is associated with high rates of seizure freedom. Complete resection, compared to subtotal resection, significantly increases the likelihood of seizure-free outcomes.
Topics: Child; Humans; Retrospective Studies; Prospective Studies; Quality of Life; Electroencephalography; Treatment Outcome; Seizures; Supratentorial Neoplasms; Brain Neoplasms
PubMed: 37707753
DOI: 10.1007/s11060-023-04446-9 -
Epilepsia Feb 2024In addition to the primary aim of seizure freedom, a key secondary aim of pediatric epilepsy surgery is to stabilize and, potentially, optimize cognitive development.... (Meta-Analysis)
Meta-Analysis Review
In addition to the primary aim of seizure freedom, a key secondary aim of pediatric epilepsy surgery is to stabilize and, potentially, optimize cognitive development. Although the efficacy of surgical treatment for seizure control has been established, the long-term intellectual and developmental trajectories are yet to be delineated. We conducted a systematic review and meta-analysis of studies reporting pre- and postsurgical intelligence or developmental quotients (IQ/DQ) of children with focal lesional epilepsy aged ≤18 years at epilepsy surgery and assessed at >2 years after surgery. We determined the IQ/DQ change and conducted a random-effects meta-analysis and meta-regression to assess its determinants. We included 15 studies reporting on 341 patients. The weighted mean age at surgery was 7.1 years (range = .3-13.8). The weighted mean postsurgical follow-up duration was 5.6 years (range = 2.7-12.8). The overall estimate of the mean presurgical IQ/DQ was 60 (95% confidence interval [CI] = 47-73), the postsurgical IQ/DQ was 61 (95% CI = 48-73), and the change was +.94 IQ/DQ (95% CI = -1.70 to 3.58, p = .486). Children with presurgical IQ/DQ ≥ 70 showed a tendency for higher gains than those with presurgical IQ/DQ < 70 (p = .059). Higher gains were determined by cessation of antiseizure medication (ASM; p = .041), not just seizure freedom. Our findings indicate, on average, stabilization of intellectual and developmental functioning at long-term follow-up after epilepsy surgery. Once seizure freedom has been achieved, ASM cessation enables the optimization of intellectual and developmental trajectories in affected children.
Topics: Child; Humans; Child, Preschool; Adolescent; Epilepsy; Epilepsies, Partial; Intelligence; Intelligence Tests; Seizures; Treatment Outcome; Retrospective Studies
PubMed: 38031640
DOI: 10.1111/epi.17834 -
The Archives of Bone and Joint Surgery 2024To compile the existing literature on bilateral anterior shoulder dislocation (BASD) and analyze patient demographics, mechanisms of injury, injury characteristics,... (Review)
Review
OBJECTIVES
To compile the existing literature on bilateral anterior shoulder dislocation (BASD) and analyze patient demographics, mechanisms of injury, injury characteristics, management, and outcome.
METHODS
This systematic review was conducted in accordance with Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) guidelines. Online databases, including Ovid Medline 1946-, Embase.com 1947-, Scopus 1960-, Cochrane Central, and Clinicaltrials.gov were systematically queried. Studies eligible for inclusion were case reports or case-series, documenting BASD. Two reviewers independently screened and applied a set of a priori exclusion criteria to each returned study. Data were extracted, compiled, and synthesized from each reported case of BASD. Contingency tables/Chi-Square Analyses, T-tests, and univariate regression analyses were conducted to assess relationships between different variables.
RESULTS
Eighty-one studies (87 cases of BASD) were included. Patients were 41.1 (SD± 19.5) years old and most were male (n=63; 72.4%). Around a quarter of patients (28.7%) had a history of epilepsy/seizures or were being worked-up for such. Younger males were more likely to have BASD due to a seizure or electrocution (P<0.05). Close to a third of cases (n=27; 31.0%) were delayed in presentation. Those sustaining seizures or electrocutions were more likely to be delayed in presentation (P=0.013). Most events resulted in simple dislocations that were closed reduced successfully. BASD resulting from seizures or electrocutions were more likely to be fracture-dislocations (P=0.018); and in younger patients with fracture-dislocations, closed reduction was more often to fail or not be attempted (P<0.05). Median follow-up was 6 months (IQR: 3 months - 12 months). Seven patients (10.6%) had complications and 4 (2.3%) demonstrated recurrent instability.
CONCLUSION
In young males presenting with BASD without known trauma, suspicion should be high for a convulsant event. In patients with a known seizure disorder who present with chronic bilateral shoulder or arm pain, BASD should be considered and work-up should be expedited to avoid misdiagnosis.
PubMed: 38817413
DOI: 10.22038/ABJS.2024.67743.3211 -
Journal of Clinical Neurophysiology :... Sep 2023In this review, authors discuss epilepsy originating from posterior cingulate regions, a challenging entity to diagnose and most likely underrecognized. A systematic...
In this review, authors discuss epilepsy originating from posterior cingulate regions, a challenging entity to diagnose and most likely underrecognized. A systematic review of posterior middle and posterior cingulate epilepsy cases was conducted to present a summary of current knowledge about this localization-based type of epilepsy. The literature search identified 32 articles, for a total of 69 patients (34 with posterior middle cingulate epilepsy [pMCE] and 35 with posterior cingulate epilepsy [PCE]). Most patients were children and young adults with drug-resistant lesional epilepsy with high seizure burden. In both groups, most patients reported auras, mainly sensory, but various types were reported, including autonomic, behavioral, and cognitive manifestations. Most pMCE and PCE showed motor manifestations (mainly respectively asymmetric tonic posturing and automotor features). Impaired awareness during seizures was more frequently reported in PCE than in pMCE. As for ictal scalp EEG, epileptogenic abnormalities were poorly lateralized and did not localize the seizure onset zone. An ictal temporal involvement was only observed in PCE. Interictal EEG findings were nonspecific. As for other presurgical noninvasive investigations, data are limited, and no studies have adequately assessed their value. Partly explained by our inclusion criteria, most patients underwent a surgical procedure (either lesionectomy or resection of epileptogenic zone as defined by intracranial EEG study results), which overall yielded good outcomes.
Topics: Child; Young Adult; Humans; Epilepsy, Frontal Lobe; Gyrus Cinguli; Seizures; Electroencephalography; Electrocorticography; Drug Resistant Epilepsy
PubMed: 36930208
DOI: 10.1097/WNP.0000000000000975 -
Journal of Neurology, Neurosurgery, and... Feb 2024Functional neurological disorder (FND) is characterised by neurological symptoms, such as seizures and abnormal movements. Despite its significance to patients, the...
BACKGROUND
Functional neurological disorder (FND) is characterised by neurological symptoms, such as seizures and abnormal movements. Despite its significance to patients, the clinical features of chronic pain in people with FND, and of FND in people with chronic pain, have not been comprehensively studied.
METHODS
We systematically reviewed PubMed, Embase and PsycINFO for studies of chronic pain in adults with FND and FND in patients with chronic pain. We described the proportions of patients reporting pain, pain rating and timing, pain-related diagnoses and responsiveness to treatment. We performed random effects meta-analyses of the proportions of patients with FND who reported pain or were diagnosed with pain-related disorders.
RESULTS
Seven hundred and fifteen articles were screened and 64 were included in the analysis. Eight case-control studies of 3476 patients described pain symptoms in a higher proportion of patients with FND than controls with other neurological disorders. A random effects model of 30 cohorts found that an estimated 55% (95% CI 46% to 64%) of 4272 patients with FND reported pain. Random effects models estimated diagnoses of complex regional pain syndrome in 22% (95% CI 6% to 39%) of patients, irritable bowel syndrome in 16% (95% CI 9% to 24%) and fibromyalgia in 10% (95% CI 8% to 13%). Five studies of FND diagnoses among 361 patients with chronic pain were identified. Most interventions for FND did not ameliorate pain, even when other symptoms improved.
CONCLUSIONS
Pain symptoms and pain-related diagnoses are common in FND. Classification systems and treatments should routinely consider pain as a comorbidity in patients with FND.
PubMed: 38383157
DOI: 10.1136/jnnp-2023-332810 -
Pediatric Neurology Jun 2024Febrile seizures (FS) are the most common neurological disorder in pediatric age. FS affect 2% to 12% of children and result from a complex interplay of genetic and... (Review)
Review
BACKGROUND
Febrile seizures (FS) are the most common neurological disorder in pediatric age. FS affect 2% to 12% of children and result from a complex interplay of genetic and environmental factors. Effective management and unambiguous recommendations are crucial for allocating health care resources efficiently and ensuring cost-effectiveness in treating FS.
METHODS
This systematic review compares existing guidelines to provide insights into FS management. Seven guidelines published between 1991 and 2021, from Japan, United Kingdom, United States, Mexico, India, and Italy, were included. Data extraction covered definitions, diagnostic criteria, hospital admission criteria, diagnostic tests, management, and prophylaxis recommendations.
RESULTS
Hospital admission criteria varied but typically included age <18 months and complex FS. Neuroimaging and lumbar puncture recommendations varied, with most guidelines suggesting limited use. Pharmacologic prophylaxis was generally discouraged for simple FS but considered only for high-risk cases, due to the benign nature of FS and the potential side effects of antiseizure medications.
CONCLUSIONS
Guidelines on FS exhibit similarities and differences, highlighting the need for standardized management and improved parental education to enhance clinical outcomes and reduce economic and social costs associated with FS. Future research should focus on creating updated international guidelines and ensuring their practical implementation.
Topics: Humans; Seizures, Febrile; Practice Guidelines as Topic; Infant
PubMed: 38653182
DOI: 10.1016/j.pediatrneurol.2024.03.024 -
The Cochrane Database of Systematic... Nov 2023Perinatal stroke refers to a diverse but specific group of cerebrovascular diseases that occur between 20 weeks of fetal life and 28 days of postnatal life. Acute... (Review)
Review
BACKGROUND
Perinatal stroke refers to a diverse but specific group of cerebrovascular diseases that occur between 20 weeks of fetal life and 28 days of postnatal life. Acute treatment options for perinatal stroke are limited supportive care, such as controlling hypoglycemia and seizures. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, or regenerate injured brain tissue. Preclinical findings have culminated in ongoing human neonatal studies.
OBJECTIVES
To evaluate the benefits and harms of stem cell-based interventions for the treatment of stroke in newborn infants compared to control (placebo or no treatment) or stem-cell based interventions of a different type or source.
SEARCH METHODS
We searched CENTRAL, PubMed, Embase, and three trials registries in February 2023. We planned to search the reference lists of included studies and relevant systematic reviews for studies not identified by the database searches.
SELECTION CRITERIA
We attempted to include randomized controlled trials, quasi-randomized controlled trials, and cluster trials that evaluated any of the following comparisons. • Stem cell-based interventions (any type) versus control (placebo or no treatment) • Mesenchymal stem/stromal cells (MSCs) of a specifictype (e.g. number of doses or passages) or source (e.g. autologous/allogeneic or bone marrow/cord) versus MSCs of another type or source • Stem cell-based interventions (other than MSCs) of a specific type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, or induced pluripotent stem cell-derived cells) or source (e.g. autologous/allogeneic or bone marrow/cord) versus stem cell-based interventions (other than MSCs) of another type or source • MSCs versus stem cell-based interventions other than MSCs We planned to include all types of transplantation regardless of cell source (bone marrow, cord blood, Wharton's jelly, placenta, adipose tissue, peripheral blood), type of graft (autologous or allogeneic), and dose.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were all-cause neonatal mortality, major neurodevelopmental disability, and immune rejection or any serious adverse event. Our secondary outcomes included all-cause mortality prior to first hospital discharge, seizures, adverse effects, and death or major neurodevelopmental disability at 18 to 24 months of age. We planned to use GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified no completed or ongoing randomized trials that met our inclusion criteria. We excluded three studies: two were phase 1 trials, and one included newborn infants with conditions other than stroke (i.e. cerebral ischemia and anemia). Among the three excluded studies, we identified the first phase 1 trial on the use of stem cells for neonatal stroke. It reported that a single intranasal application of bone marrow-derived MSCs in term neonates with a diagnosis of perinatal arterial ischemic stroke (PAIS) was feasible and apparently not associated with severe adverse events. However, the trial included only 10 infants, and follow-up was limited to three months.
AUTHORS' CONCLUSIONS
No evidence is currently available to evaluate the benefits and harms of stem cell-based interventions for treatment of stroke in newborn infants. We identified no ongoing studies. Future clinical trials should focus on standardizing the timing and method of cell delivery and cell processing to optimize the therapeutic potential of stem cell-based interventions and safety profiles. Phase 1 and large animal studies might provide the groundwork for future randomized trials. Outcome measures should include all-cause mortality, major neurodevelopmental disability and immune rejection, and any other serious adverse events.
Topics: Infant, Newborn; Pregnancy; Female; Infant; Humans; Infant Mortality; Stem Cell Transplantation; Stroke; Seizures
PubMed: 37994736
DOI: 10.1002/14651858.CD015582.pub2 -
Cannabis and Cannabinoid Research Aug 2023This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Bibliographic and clinical trial registries were searched for... (Review)
Review
This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Bibliographic and clinical trial registries were searched for interventional human trials using cutaneously administered CBD or reported plasma CBD concentrations (any species). Eight of 544 articles fitted the selection criteria: 3 placebo-controlled randomized and 5 single-arm trials. Eleven more studies were found in clinical trial databases but not accessible. Symptoms targeted were dermatopathologies or safety (two studies), pain (two), and behavior (one). Doses were 50-250 mg or 0.075-1.0% CBD, but coformulated with other ingredients. Risk of bias was high and reporting deficiencies further compromised data reliability. Diverse methodologies and formulations hampered syntheses for CBD dose, efficacy, and safety. Plasma CBD levels in dogs and rodents were 0.01-5 μM translating to <100 nM free, unbound CBD in humans. Adverse events were uncommon and mild, but meaningless without CBD's contribution to efficacy data. Achievable CBD plasma concentrations ∼100 nM can interact predominantly with high-affinity CBD targets, for example, TRPA1 and TRPM8 membrane channels that are abundantly expressed in pathological conditions. Even if reached, higher CBD concentrations on less susceptible targets risk complex and unsafe CBD therapy. A conceptual framework is proposed where dermal capillary loops create sinking for topical CBD demonstrating parallels between topical and transdermal CBD administration. Users risk generalizing inadequately designed trials to all CBD preparations. New clinical trials are urgently needed: they must demonstrate that outcomes are solely from CBD pharmacology, are reliable, unbiased, safe, and comparable. Measurements of sustained plasma CBD levels are mandatory, irrespective of administration route for successful translation from systems that express human molecular targets. Placebos must be appropriate. Transcutaneous and topical formulations need preliminary studies to optimize CBD skin penetration. Then, users can rationally balance efficacy against potential harms and cost-effectiveness of CBD formulations.
Topics: Humans; Animals; Dogs; Cannabidiol; Reproducibility of Results; Pain; Administration, Cutaneous; Seizures
PubMed: 35605018
DOI: 10.1089/can.2021.0154