OBJECTIVE: We comprehensively characterized a large pediatric cohort with focal cortical dysplasia (FCD) type 1 to expand the phenotypic spectrum and to identify predictors of postsurgical outcomes. METHODS: We included pediatric patients with histopathological diagnosis of isolated FCD type 1 and at least 1 year of postsurgical follow-up. We systematically reanalyzed clinical, electrophysiological, and radiological features. The results of this reanalysis served as independent variables for subsequent statistical analyses of outcome predictors. RESULTS: All children (N = 31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient [IQ]/developmental quotient scores = 32-106). Low presurgical IQ was associated with abnormal slow background electroencephalographic (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six of eight MRI-negative cases, fluorodeoxyglucose-positron emission tomography (PET) and subtraction ictal single photon emission computed tomography coregistered to MRI helped localize the dysplastic cortex. Sixteen patients (51.6%) underwent invasive EEG. By the last follow-up (median = 5 years, interquartile range = 3.3-9 years), seizure freedom was achieved in 71% of patients (22/31), including seven of eight MRI-negative patients. Antiseizure medications were reduced in 21 patients, with complete withdrawal in six. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI and PET findings. SIGNIFICANCE: This study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. The applied multilayered presurgical approach helped localize the epileptogenic zone in many previously nonlesional cases, resulting in improved postsurgical seizure outcomes, which are more favorable than previously reported for FCD type 1 patients.
- MeSH
- Child MeSH
- Electroencephalography * methods MeSH
- Epilepsy MeSH
- Focal Cortical Dysplasia MeSH
- Cohort Studies MeSH
- Infant MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Malformations of Cortical Development, Group I * surgery complications diagnostic imaging MeSH
- Malformations of Cortical Development surgery complications diagnostic imaging MeSH
- Adolescent MeSH
- Positron-Emission Tomography MeSH
- Child, Preschool MeSH
- Drug Resistant Epilepsy * surgery diagnostic imaging physiopathology MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVE: Epilepsy surgery in the operculoinsular cortex is challenging due to the difficult delineation of the epileptogenic zone and the high risk of postoperative deficits. METHODS: Pre- and postsurgical data from 30 pediatric patients who underwent operculoinsular cortex surgery at the Motol Epilepsy Center Prague from 2010 to 2022 were analyzed. RESULTS: Focal cortical dysplasia (FCD; n = 15, 50%) was the predominant cause of epilepsy, followed by epilepsy-associated tumors (n = 5, 17%) and tuberous sclerosis complex (n = 2, 7%). In eight patients where FCD was the most likely etiology, the histology was negative. Seven patients (23%) displayed normal magnetic resonance imaging results. Seizures exhibited diverse semiology and propagation patterns (frontal, perisylvian, and temporal). The ictal and interictal electroencephalographic (EEG) findings were mostly extensive. Multimodal imaging and advanced postprocessing were frequently used. Stereo-EEG was used for localizing the epileptogenic zone and eloquent cortex in 23 patients (77%). Oblique electrodes were used as guides for better neurosurgeon orientation. The epileptogenic zone was in the dominant hemisphere in 16 patients. At the 2-year follow-up, 22 patients (73%) were completely seizure-free, and eight (27%) experienced a seizure frequency reduction of >50% (International League Against Epilepsy class 3 and 4). Fourteen patients (47%) underwent antiseizure medication tapering; treatment was completely withdrawn in two (7%). Nineteen patients (63%) remained seizure-free following the definitive outcome assessment (median = 6 years 5 months, range = 2 years to 13 years 5 months postsurgery). Six patients (20%) experienced corona radiata or basal ganglia ischemia; four (13%) improved to mild and one (3%) to moderate hemiparesis. Two patients (7%) operated on in the anterior insula along with frontotemporal resection experienced major complications: pontine ischemia and postoperative brain edema. SIGNIFICANCE: Epilepsy surgery in the operculoinsular cortex can lead to excellent patient outcomes. A comprehensive diagnostic approach is crucial for surgical success. Rehabilitation brings a great chance for significant recovery of postoperative deficits.
- MeSH
- Child MeSH
- Electroencephalography * MeSH
- Epilepsy surgery diagnostic imaging MeSH
- Cohort Studies MeSH
- Infant MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Malformations of Cortical Development surgery complications diagnostic imaging MeSH
- Adolescent MeSH
- Cerebral Cortex diagnostic imaging surgery MeSH
- Neurosurgical Procedures methods MeSH
- Child, Preschool MeSH
- Retrospective Studies MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Modafinil is primarily used to treat narcolepsy but is also used as an off-label cognitive enhancer. Functional magnetic resonance imaging studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug's effects on subcortical structures. Following preliminary findings, we evaluated modafinil's activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters. METHODS: Patterns of resting-state functional magnetic resonance imaging connectivity were estimated in 50 participants from scans acquired pre- and postadministration of a single (100 mg) dose of modafinil (n = 25) or placebo (n = 25). Using specific cerebellar regions as seeds for voxelwise analyses, we examined modafinil's modulation of cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases. RESULTS: Modafinil increased the connectivity of crus I and vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D2 receptors. The vermis I-II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H3 receptors. The vermis VII-VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission. CONCLUSIONS: Our study reveals modafinil's modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves crus I and the vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors.
- MeSH
- Adult MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Young Adult MeSH
- Modafinil * pharmacology administration & dosage MeSH
- Cerebellum * drug effects diagnostic imaging metabolism MeSH
- Neocortex drug effects metabolism diagnostic imaging MeSH
- Neural Pathways drug effects metabolism MeSH
- Wakefulness-Promoting Agents pharmacology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
INTRODUCTION: Alopecia areata is a common autoimmune disease which results in reversible hair loss. Janus kinase inhibitors are prescribed for severe alopecia areata with encouraging results. There are no studies comparing the efficacy and safety of Janus kinase inhibitors to traditional treatment options, such as topical immunomodulators and traditional immunosuppressants. AIMS: To retrospectively compare the efficacy and safety of baricitinib, an approved Janus kinase inhibitor, to other treatments for severe AA during a 6-month treatment period. MATERIALS/METHODS: We included patients with newly presenting, relapsing or treatment-resistant alopecia areata with Severity of Alopecia Tool (SALT) score ≥ 50, for the period between July 2021 and July 2023. Medical histories were reviewed and possible side effects were recorded. Primary endpoints were SALT ≤ 20 and SALT ≤ 10 after 6 months of treatment. RESULTS: Seventy-five patients (53 females) were divided into three groups: topical immunomodulators (51 patients); baricitinib (19 patients); and a group receiving pulsed intramuscular corticosteroids or traditional immunosuppressants (11 patients). Twenty-one patients received more than one treatment options within 2 years. After 6 months, the baricitinib group showed superior efficacy with 32% and 26% of patients achieving SALT ≤ 20 and SALT ≤ 10, compared to 12% and 9% in both other groups. Baricitinib demonstrated better secondary outcomes (50% and 90% reduction from initial SALT scores). All treatments exhibited mild-to-moderate and expected side effects. Weight gain, which had not been reported in clinical trials for alopecia areata, was observed in three baricitinib-treated patients. CONCLUSION: Baricitinib was superior to traditional treatments for severe alopecia areata after 6 months. Weight gain concerned 16% of patients receiving baricitinib.
- MeSH
- Alopecia Areata * drug therapy MeSH
- Azetidines * adverse effects therapeutic use administration & dosage MeSH
- Adult MeSH
- Adrenal Cortex Hormones therapeutic use administration & dosage adverse effects MeSH
- Immunologic Factors administration & dosage adverse effects therapeutic use MeSH
- Immunosuppressive Agents * adverse effects therapeutic use administration & dosage MeSH
- Janus Kinase Inhibitors * adverse effects administration & dosage therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Purines * adverse effects administration & dosage therapeutic use MeSH
- Pyrazoles * adverse effects administration & dosage therapeutic use MeSH
- Retrospective Studies MeSH
- Severity of Illness Index * MeSH
- Sulfonamides * adverse effects administration & dosage therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
The small airways, also referred to as the lung's silent zone, are closely associated with poor symptom control and more frequent asthma exacerbations. The oscillometry technique superimposes sound or airwaves onto normal tidal breathing and provides information on resistance and reactance, that is, obstacles to airflow occurring inside and outside of the bronchi. More recently, a management paradigm based on so-called "treatable traits" has been proposed to personalize and improve asthma care for individuals by proactively identifying and targeting modifiable pulmonary, extrapulmonary, and behavioral traits affecting asthma control. In this review article, we evaluate the literature on small airways dysfunction as a potential treatable trait in persistent asthma. In particular, we discuss whole- and intrabreath oscillometry and the impact of extrafine inhaled corticosteroids and systemic biologics on the peripheral airways.
- MeSH
- Asthma * physiopathology drug therapy diagnosis MeSH
- Adrenal Cortex Hormones therapeutic use MeSH
- Humans MeSH
- Oscillometry * methods MeSH
- Lung physiopathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a high recurrence rate after surgical therapy with curative intent. Adjuvant radiotherapy (RT) and mitotane therapy have been proposed as options following the adrenalectomy. However, the efficacy of adjuvant RT or mitotane therapy remains controversial. We aimed to evaluate the efficacy of adjuvant therapy in patients who underwent adrenalectomy for localised ACC. The PubMed, Scopus, and Web of Science databases were queried on March 2024 for studies evaluating adjuvant therapies in patients treated with surgery for localized ACC (PROSPERO: CRD42024512849). The endpoints of interest were overall survival (OS) and recurrence-free survival (RFS). Hazard ratios (HR) with 95% confidence intervals (95%CI) were pooled in a random-effects model meta-analysis. One randomized controlled trial (n = 91) and eleven retrospective studies (n = 4,515) were included. Adjuvant mitotane therapy was associated with improved RFS (HR: 0.63, 95%CI: 0.44-0.92, p = 0.016), while adjuvant RT did not reach conventional levels of statistical significance (HR:0.79, 95%CI:0.58-1.06, p = 0.11). Conversely, Adjuvant RT was associated with improved OS (HR:0.69, 95%CI:0.58-0.83, p<0.001), whereas adjuvant mitotane did not (HR: 0.76, 95%CI: 0.57-1.02, p = 0.07). In the subgroup analyses, adjuvant mitotane was associated with better OS (HR:0.46, 95%CI: 0.30-0.69, p < 0.001) and RFS (HR:0.56, 95%CI: 0.32-0.98, p = 0.04) in patients with negative surgical margin. Both adjuvant RT and mitotane were found to be associated with improved oncologic outcomes in patients treated with adrenalectomy for localised ACC. While adjuvant RT significantly improved OS in general population, mitotane appears as an especially promising treatment option in patients with negative surgical margin. These data can support the shared decision-making process, better understanding of the risks, benefits, and effectiveness of these therapies is still needed to guide tailored management of each individual patient.
- MeSH
- Chemotherapy, Adjuvant MeSH
- Radiotherapy, Adjuvant methods MeSH
- Adrenalectomy * methods MeSH
- Adrenocortical Carcinoma * therapy drug therapy radiotherapy MeSH
- Adrenal Cortex Neoplasms * therapy drug therapy surgery radiotherapy MeSH
- Antineoplastic Agents, Hormonal * therapeutic use MeSH
- Humans MeSH
- Mitotane * therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Review MeSH
- Systematic Review MeSH
Adrenal insufficiency (AI) manifests as a clinical syndrome arising from either the direct impairment of adrenal glands, leading to primary AI characterized by deficiencies in glucocorticoids and mineralocorticoids, or adrenal cortex atrophy due to diminished adrenocorticotropic hormone (ACTH) stimulation, a consequence of hypothalamic and/or pituitary damage, resulting in secondary AI. The diagnosis of AI is based on clinical assessment and biochemical tests, including basal hormone level measurements and stimulation tests. In evaluating the results of laboratory tests, it is necessary to consider factors that may influence both pre-analytical and analytical phases, as well as the chosen methodology. Correct diagnosis of adrenal insufficiency and timely initiation of suitable replacement therapy are paramount. These steps are crucial not only for managing the condition but also to avert potentially life-threatening adrenal crises.
- MeSH
- Adrenal Insufficiency * diagnosis etiology MeSH
- Adrenocorticotropic Hormone MeSH
- Glucocorticoids MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. Moreover, chemogenetic analysis revealed central amygdala as critical for linking appetitive emotional states with spatial contexts. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.
- MeSH
- Amphetamine pharmacology MeSH
- Amygdala physiology MeSH
- Hippocampus * physiology MeSH
- Memory Consolidation * physiology MeSH
- Rats MeSH
- Brain physiology MeSH
- Neurons physiology metabolism MeSH
- Nucleus Accumbens * physiology MeSH
- Reward * MeSH
- Memory physiology MeSH
- Cues MeSH
- Prefrontal Cortex physiology MeSH
- Mental Recall * physiology MeSH
- Machine Learning MeSH
- Ventral Tegmental Area * physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
[Glucocorticoids from a pathophysiological perspective]
Glukokortikoidy jsou hormony kůry nadledvin, jejichž syntetické deriváty jsou zejména díky svým protizánětlivým a imunosupresivním účinkům hojně užívaným lékem v klinické praxi. při jejich podávání však může dojít ke vzniku tzv. hyperkortizolismu, jehož klinické příznaky se podobají důsledkům nadprodukce endogenních glukokortikoidů. předkládaný článek přibližuje patofyziologický podklad glukokortikoidy vyvolaných změn u pediatrických pacientů, jejichž porozumění je zásadní pro správnou léčebnou praxi
Glucocorticoids are hormones of the adrenal cortex, whose synthetic derivatives are widely used in the therapy of various diseases, mainly due to their anti-inflammatory and immunosuppressive effects. However, their administration may result in so-called hypercortisolism, the clinical symptoms of which resemble the consequences of overproduction of endogenous glucocorticoids. this article presents the pathophysiological background of glucocorticoid induced changes in pediatric patients, the understanding of which is essential for proper therapeutic practice.
- MeSH
- Cushing Syndrome chemically induced diagnosis physiopathology MeSH
- Child MeSH
- Glucocorticoids * pharmacology blood metabolism therapeutic use MeSH
- Hyperglycemia chemically induced diagnosis MeSH
- Humans MeSH
- Medication Therapy Management MeSH
- Drug-Related Side Effects and Adverse Reactions diagnosis drug therapy classification MeSH
- Obesity chemically induced diagnosis MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Review MeSH
Hypokortikalismus, též adrenokortikální insuficience (AI), je stav, kdy kůra nadledvin neprodukuje dostatečné množství hormonů, zejména kortizolu. Postupně se rozvíjející insuficience může hlavně u seniorů unikat pozornosti, a to pro své nespecifické příznaky, které mohou být snadno zaměněny za jiné zdravotní problémy spojené s věkem. V této kazuistice je prezentován případ pacientky, u které se rozvinul funkční hypokortikalismus po krátkodobé terapii vysokými dávkami glukokortikoidů v rámci léčby covidu-19. Pacientka byla opakovaně vyšetřována pro nespecifické potíže zahrnující kolapsové stavy při hypotenzi a nechutenství s následným váhovým úbytkem. K odhalení správné diagnózy nakonec vedl opakovaný nález hyponatremie. Po zahájení terapie se stav pacientky výrazně zlepšil.
Hypocortical insufficiency (AI) is a condition in which the adrenal cortex does not produce sufficient amounts of hormones, especially cortisol. Gradually developing insufficiency can go unnoticed, especially in the elderly, due to its nonspecific symptoms that can easily be mistaken for other age-related health problems. This case report presents the case of a patient who developed functional hypocorticism after short-term therapy with high doses of glucocorticoids as part of the treatment of covid-19. The patient was repeatedly examined for nonspecific problems including collapse states with hypotension and anorexia with subsequent weight loss. The correct diagnosis was finally revealed by repeated findings of hyponatremia. After starting therapy, the patient‘s condition improved significantly.