Large (≥3-Millimeter) Parenchymal Brain Calcified Cysticerci Are More Often Associated with Hippocampal Atrophy than Smaller Ones in Seizure-Free Individuals with a Single Lesion.

Calcified cysticerci are often associated with hippocampal atrophy (HA). While most studies suggest that repetitive seizures cause HA in these patients, others have demonstrated that HA may also occur in persons without epilepsy. Little is known about mechanisms triggering HA in seizure-free individuals with calcified cysticerci. Here, we aimed to assess whether the size of the calcification is associated with HA. Using a population-based design, we selected apparently seizure-free individuals with a single calcified cysticercus in whom interictal paroxysmal activity and other causes of HA have been discarded. A total of 55 individuals (mean age, 58.3 ± 13 years, 62% women) fulfilled inclusion criteria. Unadjusted and multivariate models were fitted to assess the association between the size of the calcification dichotomized into <3 mm and ≥3 mm (exposure) and the presence of HA (outcome). Sixteen participants (29%) had HA, which was asymmetric in eight (50%) cases. Hippocampal atrophy was noted in 11/20 (55%) participants with large calcifications and in 5/35 (14%) with small calcifications (P = 0.001). A multivariate logistic regression model showed a significant association between the presence of large calcifications and HA, after adjustment for relevant confounders (odds ratio: 7.78; 95% CI: 1.72-35.1). Participants with calcifications ≥3 mm in diameter were 7.8 times more likely to have HA than those with smaller ones. Study results open avenues of research for the use of agents to prevent HA progression.

The effects of various therapies on vulvovaginal atrophy and quality of life in gynecological cancer patients: a systematic review.

PURPOSE: Tumors affecting the female genital tract and their treatments have the potential to induce adverse modifications in vaginal health and impact personal aspects of patient's lives. Vulvovaginal atrophy is one of the morphological changes observed in individuals with a history of gynecological cancer, influenced both by the biological environment of tumors and the main therapeutic modalities employed. Therefore, the purpose of this study was to identify approaches to treat vulvovaginal atrophy while assessing the impact on the emotional and sexual health of women diagnosed with gynecological cancers. METHODS: To achieve this goal, a systematic review was conducted following the methodological guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The databases used for literature research were PubMed and Web of Science. RESULTS: Initially, 886 articles were obtained. After eliminating duplicates and applying inclusion/exclusion criteria, seven articles were selected for analysis. The period of highest publication activity spanned from 2017 to 2020, with the majority conducted in Italy. Five treatment modalities were identified and categorized as vaginal suppository, oral medication, surgical procedure, CO2 laser therapy, and vaginal dilator. Twenty-four outcomes related to vaginal health and 30 outcomes related to overall, sexual, and emotional quality of life were analyzed. CONCLUSION: In general, all interventions demonstrated the ability to improve vaginal health or, at the very least, the sexual health of patients. Thus, despite limitations, all treatments have the potential to address vulvovaginal atrophy in patients with a history of gynecological cancer.

Analysis of the atrophic mandible rehabilitated with fixed total prosthesis on mono or bicortical implants.

Rehabilitation of edentulous atrophic mandibles involves the placement of implants in the anterior segment of the mandible. The primary stability of these implants can be improved using the base of the mandible as complementary anchorage (bicorticalization). This study aimed to analyze the biomechanics of atrophic mandibles rehabilitated with monocortical or bicortical implants. Two three-dimensional virtual models of edentulous mandibles with severe atrophy were prepared. Four monocortical implants were placed in one model (McMM), and four bicortical implants were placed in the other (BcMM). An implant-supported total prosthesis was prepared for each model. Then, a total axial load of 600 N was applied to the posterior teeth, and its effects on the models were analyzed using finite element analysis. The highest compressive stresses were concentrated in the cervical region of the implants in the McMM (-32.562 Mpa); in the BcMM, compressive stresses were distributed in the upper and lower cortex of the mandible, with increased compressive stresses at the distal implants (-63.792 Mpa). Thus, we conclude that axial loading forces are more uniformly distributed in the peri-implant bone when using monocortical implants and concentrated in the apical and cervical regions of the peri-implant bone when using bicortical implants.

Photobiomodulation minimizes taste changes during hematopoietic cell transplantation: A randomized clinical trial.

Prevention and treatment protocols for taste changes observed during hematopoietic cell transplantation (HCT) are not well-established. The purpose of this study was to assess the efficacy of photobiomodulation (PBM) in relieving taste changes and preventing lingual papillae atrophy. HCT patients received PBM (n = 42) on the tongue dorsum using an InGaAIP laser (660 nm, 100 mW, 1.1 W/cm2, 8.8 J/cm2). During the HCT conditioning (T0), severe neutropenia (T1), and after neutrophil engraftment (T2), taste acuity for sweet, bitter, sour, and salty solutions, and clinical appearance of lingual papillae were compared with those of a placebo group (n = 43). PBM significantly reduced hypogeusia, ageusia, and parageusia at T1 and T2, and also successfully prevented papillae atrophy during all the analyzed HCT periods. In conclusion, PBM enhanced taste acuity during HCT. The decrease in papillae atrophy indicated a potential regenerative effect of this therapy on tongue mucosa.

Gender affirming hormone therapy and transgender women fertility: Histologic predictors of germ cell presence.

Objective: Evaluate histological changes in testicular parameters after hormone treatment in transgender women. Methods: Cross-section study with patients who underwent gonadectomy at Hospital de Clínicas de Porto Alegre from 2011 to 2019. Hormone treatment type, route of administration, age at initiation and duration were recorded. Atrophy parameters were observed: testicular volume, tubular diameter, basal membrane length, presence of spermatogonia and spermatids (diploid and haploid spermatozoid precursors). Results: Eighty-six patients were included. Duration of hormone treatment is associated with testicular atrophy and spermatogenesis arrest. Other characteristics of hormone treatment such as age of initiation, route of administration and type of treatment were not associated with testicular histological changes. Testicular volume may predict spermatogenesis arrest. Basal membrane length and tubular diameter ratio is an interesting predictor of germ cell presence. Conclusion: Cross-sex hormone treatment affects testicular germ cell presence. Basal membrane length and tubular diameter ratio reduces inter variability of measurements and better exemplify how atrophic seminiferous tubules are. Fertility preservation should be addressed by healthcare providers in order to recognize gender affirming treatment impact on transgender health.

Basal forebrain volume and metabolism in carriers of the Colombian mutation for autosomal dominant Alzheimer's disease.

We aimed to study atrophy and glucose metabolism of the cholinergic basal forebrain in non-demented mutation carriers for autosomal dominant Alzheimer's disease (ADAD). We determined the level of evidence for or against atrophy and impaired metabolism of the basal forebrain in 167 non-demented carriers of the Colombian PSEN1 E280A mutation and 75 age- and sex-matched non-mutation carriers of the same kindred using a Bayesian analysis framework. We analyzed baseline MRI, amyloid PET, and FDG-PET scans of the Alzheimer's Prevention Initiative ADAD Colombia Trial. We found moderate evidence against an association of carrier status with basal forebrain volume (Bayes factor (BF10) = 0.182). We found moderate evidence against a difference of basal forebrain metabolism (BF10 = 0.167). There was only inconclusive evidence for an association between basal forebrain volume and delayed memory and attention (BF10 = 0.884 and 0.184, respectively), and between basal forebrain volume and global amyloid load (BF10 = 2.1). Our results distinguish PSEN1 E280A mutation carriers from sporadic AD cases in which cholinergic involvement of the basal forebrain is already detectable in the preclinical and prodromal stages. This indicates an important difference between ADAD and sporadic AD in terms of pathogenesis and potential treatment targets.

Leptin receptor reactivation restores brain function in early-life Lepr-deficient mice.

Obesity is a chronic disease caused by excessive fat accumulation that impacts the body and brain health. Insufficient leptin or leptin receptor (LepR) is involved in the disease pathogenesis. Leptin is involved with several neurological processes, and it has crucial developmental roles. We have previously demonstrated that leptin deficiency in early life leads to permanent developmental problems in young adult mice, including an imbalance in energy homeostasis, alterations in melanocortin and the reproductive system and a reduction in brain mass. Given that in humans, obesity has been associated with brain atrophy and cognitive impairment, it is important to determine the long-term consequences of early-life leptin deficiency on brain structure and memory function. Here, we demonstrate that leptin-deficient (LepOb) mice exhibit altered brain volume, decreased neurogenesis and memory impairment. Similar effects were observed in animals that do not express the LepR (LepRNull). Interestingly, restoring the expression of LepR in 10-week-old mice reverses brain atrophy, in addition to neurogenesis and memory impairments in older animals. Our findings indicate that leptin deficiency impairs brain development and memory, which are reversible by restoring leptin signalling in adulthood.

[Ipsilateral ureteroureterostomy. A safe alternative in complete duplicated collecting system with associated pathology]. / Uretero-ureteroanastomosis distal ipsilateral. Una alternativa segura en doble sistema renal completo con patología asociada.

In patients with complete double renal system with the involvement of only one system, there are several surgical alternatives for its resolution. Uretero-ureteral anastomosis has been presented as a good alternative, even in cases with atrophy of the affected system. OBJECTIVE: To report our experience in patients with complete double renal system with only one system affected, with the surgical technique of uretero-ureteral anastomosis. PATIENTS AND METHOD: Retrospective study of patients with double renal system with involvement of one of the systems, treated with uretero-ureteral anastomosis technique between January 2015 and May 2022. The variables of age, specific pathology of the affected system, preoperative study, days of hospitalization, postoperative complications (leakage, obstruction, infection), and follow-up time were evaluated. RESULTS: We analyzed 26 procedures in 25 patients, mean age 36.8 months (range: 8-80); 53.8% had ectopic ureter, 23% ureterocele, 11.5% sphincteric ureterocele, and 11.5% VUR of the lower system. All were studied preoperatively with urethrocystography and 65% with scintigraphy. 50% of the operated systems showed signs of renal atrophy. The average hospital stay was 2.2 days (range: 1-7). In an average follow-up of 26.5 months (range: 3-77), one patient presented leakage, no patient presented signs suggestive of obstruction, and one patient presented febrile urinary tract infection with persistent lower-grade reflux. CONCLUSION: In our experience, the uretero-ureteral anastomosis technique proved to be an easy and safe alternative to reproduce, with a success rate of 96%, 11% of grade I complications, and 4% of grade II complications according to the Clavien-Dindo classification.

Macular atrophy and focal choroidal excavation in a patient with JAG1- related alagille syndrome.

INTRODUCTION: Alagille syndrome (AGS) is a genetic disease with multisystemic affection, including ocular manifestations. Recently, a high frequency of posterior segment findings, including macular changes, has been reported. This publication aims to report an unusual finding of macular atrophy and a focal choroidal excavation in a patient with JAG1 related AGS. METHODS: Case report. RESULTS: This publication describes an atypical presentation of focal choroidal excavation (FCE) and unilateral macular atrophy in a 7-year-old male with Alagille syndrome (AGS). Genetic analysis revealed a pathogenic variant in the JAG1 gene. Ophthalmological examination and imaging findings demonstrated characteristic ocular manifestations of AGS, including posterior embryotoxon, chorioretinal atrophy, and thinning of the choroid. CONCLUSION: The presence of FCE in AGS is uncommon, and the underlying mechanisms remain unclear. Further exploration of similar cases is necessary to better understand the evolution and visual prognosis in patients with AGS and FCE.

This case report highlights the presence of focal choroidal excavation and unilateral macular atrophy in a patient with Alagille syndrome. The genetic analysis identified a pathogenic variant in the JAG1 gene.

Childhood-onset Huntignton´s disease. A rare presentation. / Enfermedad de Huntington de inicio en la infancia. Una presentación poco frecuente.

INTRODUCTION: Huntington's disease (HD) is a rare autosomal dominant disease caused by the expansion of CAG triplets in the gene that encodes huntingtin. There are earlier symptoms' onset in offspring due to the phenomenon of anticipation. The clinical features of childhood-onset HD, before age 10 years, differs from adult-onset form. It is characterized by motor impairment, behavioral difficulties and delay or regression in areas of development; while chorea is rarely seen. In this case we describe clinical aspects of a patient with childhood-onset Huntington's disease. CASE REPORT: A 5-year-old girl with a family history of HD and typical development up to 3 years of age. She progressively acquired language impairment with skills that were below her age in expressive and receptive areas, without deficits in pragmatic and social skills. Regarding motor skills, she manifested instability at walking and standing, with rigidity, dystonia and choreic movements. Atrophy of the basal ganglia was evident on MRI, EEG was normal, and molecular confirmation of CAG triplet revealed repeat length of 51 copies. CONCLUSION: Childhood-onset HD differs from adult-form´s clinical manifestations. It should be considered in patients with progressive motor and cognitive impairment. Due to family inheritance, it is important to carefully examine family history and take it into account even without relatives affected, considering the anticipation phenomenon.

TITLE: Enfermedad de Huntington de inicio en la infancia. Una presentación poco frecuente.Introducción. La enfermedad de Huntington (EH) es una enfermedad de herencia autosómica dominante caracterizada por la expansión de tripletes de citosina-adenina-guanina (CAG) en el gen que codifica la huntingtina. Los síntomas en la descendencia suelen ser más tempranos por el fenómeno de anticipación. La clínica de inicio en la infancia, antes de los 10 años, difiere de la observada en la adultez. Se manifiesta por afectación motora, dificultades conductuales y retraso o regresión del desarrollo. La corea es infrecuente. El objetivo del caso es describir aspectos clínicos de una paciente con EH de inicio infantil. Caso clínico. Niña de 5 años con antecedentes familiares de EH y desarrollo típico hasta los 3 años. Presentó progresivamente afectación del lenguaje con habilidades descendidas para su edad en aspectos expresivos y comprensivos, sin afectación en las habilidades pragmáticas y sociales. En cuanto a la motricidad, la marcha y la bipedestación eran inestables, y mostraba rigidez, distonía y movimientos coreicos. Presentó atrofia de los núcleos lenticulares y caudados en la resonancia magnética, y posteriormente se realizó el diagnóstico molecular con la expansión de tripletes CAG (51 copias). Conclusión. La EH de inicio en la infancia presenta manifestaciones clínicas distintas a la forma del adulto. Debe considerarse en pacientes con afectación motora y cognitiva progresiva. Por la herencia familiar, es importante interrogar cuidadosamente sobre los antecedentes familiares y tenerla en cuenta aun sin familiares afectados por el fenómeno de anticipación.

Neuroinflammation, blood-brain barrier dysfunction, hippocampal atrophy and delayed neurodevelopment: Contributions for a rat model of congenital Zika syndrome.

The congenital Zika syndrome (CZS) has been characterized as a set of several brain changes, such as reduced brain volume and subcortical calcifications, in addition to cognitive deficits. Microcephaly is one of the possible complications found in newborns exposed to Zika virus (ZIKV) during pregnancy, although it is an impacting clinical sign. This study aimed to investigate the consequences of a model of congenital ZIKV infection by evaluating the histopathology, blood-brain barrier, and neuroinflammation in pup rats 24 h after birth, and neurodevelopment of the offspring. Pregnant rats were inoculated subcutaneously with ZIKV-BR at the dose 1 × 107 plaque-forming unit (PFU mL-1) of ZIKV isolated in Brazil (ZIKV-BR) on gestational day 18 (G18). A set of pups, 24 h after birth, was euthanized. The brain was collected and later evaluated for the histopathology of brain structures through histological analysis. Additionally, analyses of the blood-brain barrier were conducted using western blotting, and neuroinflammation was assessed using ELISA. Another set of animals was evaluated on postnatal days 3, 6, 9, and 12 for neurodevelopment by observing the developmental milestones. Our results revealed hippocampal atrophy in ZIKV animals, in addition to changes in the blood-brain barrier structure and pro-inflammatory cytokines expression increase. Regarding neurodevelopment, a delay in important reflexes during the neonatal period in ZIKV animals was observed. These findings advance the understanding of the pathophysiology of CZS and contribute to enhancing the rat model of CZS.

Comparison of the effect of noninvasive radiofrequency with vaginal estrogen and vaginal moisturizer in the treatment of vulvovaginal atrophy in postmenopausal women: a randomized clinical trial.

OBJECTIVE: To compare the effect of noninvasive radiofrequency (RF) with vaginal estrogen (E), and vaginal moisturizer (M) on improving vulvovaginal atrophy (VVA) in women with genitourinary syndrome of menopause. METHODS: A total of 32 postmenopausal women who met the inclusion criteria were randomized into three intervention arms to receive one of the following treatments: three sessions of noninvasive RF therapy (RF arm); intravaginal estriol cream 1 mg applied daily for 2 weeks, followed by 1 mg applied two times weekly or 1 mg of estradiol vaginal fast-dissolving film applied daily for 2 weeks, followed by 1 mg applied two times weekly (E arm); and intravaginal moisturizer two times a week (M arm). Assessments at baseline and after 4 months were conducted using Vaginal Health Index score, Vaginal Maturation, visual analog scale for VVA symptoms (dyspareunia, dryness, and burning), and Menopause Rating Scale (MRS) for urogenital symptoms. Vaginal wall biopsies were administered to participants who consented, pretreatment and posttreatment (at baseline and after 4 months of follow-up). RESULTS: After 4 months, the Vaginal Health Index showed an increase of 6.6 points in mean total score in the RF arm, also in the E arm (+7.3 points), with no significant improvement in the M arm (+1.5 points) (interaction effect: RF, E ≠ M, P < 0.001). Regarding vaginal maturation, there was a significant increase in superficial cells in the E arm (+31.3), with no significant changes in the RF (+9.3) and M (-0.5) arms (interaction effect: E ≠ M, P < 0.001). Vaginal pH decreased significantly in the E arm (-1.25), with a similar response in the RF arm (-1.7), with no significant improvement in the M arm (-0.25) (interaction effect: RF, E ≠ M, P < 0.001).There was a significant improvement in the MRS score for VVA symptoms in the three intervention arms, with no predominance of any arm, whereas the improvement in the total MRS score for urogenital symptoms showed a predominance of the RF arm (ΔRF: -7.8; ΔE: -3.5; ΔM: -2.3; RF ≠ E, M). According to histopathologic analysis, there was no statistically significant increase in glycogenation ( P = 0.691) or epithelial cone height ( P = 0.935), despite an increase in the median delta (difference between pretreatment and posttreatment) in the three intervention arms (glycogenation: RF arm Δ = +118.4%; E arm Δ = +130.9%; M arm Δ = +24.9%; epithelial cone height: RF arm Δ = +33.5%; E arm Δ = +18.6%; M arm Δ = +22.3%). CONCLUSION: The effect of noninvasive RF on the treatment of vulvovaginal symptoms of genitourinary syndrome of menopause was similar to vaginal estrogen, except for hormonal cytology, and superior to vaginal moisturizer, with improvement in some histomorphometric parameters. These findings are promising, especially for the population that cannot or prefers not to use vaginal estrogen therapy.

Cranial Nerve Thinning Distinguishes RFC1-Related Disorder from Other Late-Onset Ataxias.

BACKGROUND: RFC1-related disorder (RFC1/CANVAS) shares clinical features with other late-onset ataxias, such as spinocerebellar ataxias (SCA) and multiple system atrophy cerebellar type (MSA-C). Thinning of cranial nerves V (CNV) and VIII (CNVIII) has been reported in magnetic resonance imaging (MRI) scans of RFC1/CANVAS, but its specificity remains unclear. OBJECTIVES: To assess the usefulness of CNV and CNVIII thinning to differentiate RFC1/CANVAS from SCA and MSA-C. METHODS: Seventeen individuals with RFC1/CANVAS, 57 with SCA (types 2, 3 and 6), 11 with MSA-C and 15 healthy controls were enrolled. The Balanced Fast Field Echo sequence was used for assessment of cranial nerves. Images were reviewed by a neuroradiologist, who classified these nerves as atrophic or normal, and subsequently the CNV was segmented manually by an experienced neurologist. Both assessments were blinded to patient and clinical data. Non-parametric tests were used to assess between-group comparisons. RESULTS: Atrophy of CNV and CNVIII, both alone and in combination, was significantly more frequent in the RFC1/CANVAS group than in healthy controls and all other ataxia groups. Atrophy of CNV had the highest sensitivity (82%) and combined CNV and CNVIII atrophy had the best specificity (92%) for diagnosing RFC1/CANVAS. In the quantitative analyses, CNV was significantly thinner in the RFC1/CANVAS group relative to all other groups. The cutoff CNV diameter that best identified RFC1/CANVAS was ≤2.2 mm (AUC = 0.91; sensitivity 88.2%, specificity 95.6%). CONCLUSION: MRI evaluation of CNV and CNVIII using a dedicated sequence is an easy-to-use tool that helps to distinguish RFC1/CANVAS from SCA and MSA-C.

A simple drug-delivery microneedling technique modality successfully improves linear atrophic scars.

BACKGROUND: Atrophic scars are white, dermal depressions, caused by the destruction of collagen fibers and decrease in epidermal cells, following inflammation after different types of trauma. They lead to significant physical, aesthetic and psychological barriers and their treatment remain a therapeutic challenge for dermatologists. Microneedling has been shown to improve scars by stimulating angiogenesis and neocolagenesis and the combination of anti-fibrotic drugs could potentialize the results. METHODS: We present 8 cases of patients with linear scars, successfully treated with two sessions of a new Microneedling technique, using a tattoo machine, associated with drug delivery of 5-FU. RESULTS: A marked improvement in scar pigmentation and texture were noted by patients and doctors, 6 months following the sessions of MMP and drug delivery with 5-FU, in different body sites. We also showed that the assessment scores of at least one of the professionals with those of the patient had significant correlations with each other, which shows consistency between the qualitative assessment instruments. We also showed that the cause of the injury can influence joint assessment scores (physicians plus patient) or those exclusive to professionals trained for the assessments, generating evidence that the cause of the injury can influence the treatment outcome itself. CONCLUSIONS: We present an inexpensive and promising approach that can be easily done as an in-office procedure. Larger, multicenter studies are needed to validate this technique among the first line therapies for acne scar treatment.

Clinical outcomes following atrophic alveolar ridge reconstruction using collagenated xenogeneic bone block or autogenous bone block: One-year follow-up of a randomized controlled clinical.

AIM: This investigation aimed to evaluate the 1-year survival of implants placed after staged lateral alveolar ridge augmentation using equine-derived collagenated xenogeneic bone blocks (CXBBs) or autogenous bone block (ABB). MATERIALS AND METHODS: Fifty patients who underwent lateral augmentation in a previous trial were included. The primary outcome measure was implant survival at the 1-year follow-up, and secondary outcomes included implant success, peri-implant clinical and volumetric parameters, pink aesthetic scores (PES) and patient-reported outcome measures. Data analysis involved Fisher's exact test, the Mann-Whitney U-test and the Wilcoxon signed-rank test. RESULTS: In this study, no late implant failures were observed. The cumulative survival rates were 78.6% for the CXBB group and 90.9% for the ABB group, with no difference between the groups. Similarly, the success rates were 53.6% and 63.6%, respectively, showing no significant difference. Peri-implant clinical and volumetric parameters indicated the presence of healthy peri-implant tissues surrounding implants placed in both CXBB- and ABB-augmented sites. PES were 8.5 and 11.0 for implants placed in CXBB- and ABB-augmented sites, respectively. Furthermore, patient satisfaction rates were high and similar between the groups. CONCLUSIONS: Dental implants placed in both CXBB- and ABB-augmented ridges demonstrated no statistically significant differences in clinical, volumetric and aesthetic outcomes, along with high patient satisfaction rates.

Treatment of Atrophy of the Labia Majora: Calcium Hydroxyapatite or Hyaluronic Acid?

PURPOSE: The study aimed to evaluate and compare the efficacy and safety of treating atrophied labia majora with hyaluronic acid (HA) and calcium hydroxyapatite (CaHA). METHODS: Ten participants complaining of sagging or loss of volume in the labia majora were evaluated and randomly assigned to two groups-treated with CaHA or AH. Photographic documentation was taken and appreciated by the participants and by blind observers. RESULTS: The study showed an improvement in labia majora regarding volumization and flaccidity that was more significant after 90 days of treatment in both treatments. Besides flaccidity, volume replacement resulted in better balance and proportion between the labia majora and labia minora. The evaluators, independent and blind, judged that in 80% of the cases of the HA group and in 50% of cases of the CaHA group, there was an excellent improvement. CONCLUSION: CaHA and HA are both effective and safe for treating the intimate region, and this study cannot prove the superiority of one over the other. An appropriate assessment involving the analysis of sagging and/or volume loss and the creation of a sequential treatment protocol, involving CaHA and HA, seems to be the best solution. LEVEL OF EVIDENCE I: Evidence obtained from at least one properly designed randomized controlled trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Cerebral hemiatrophy and hemiparesis following hemiclonic status epilepticus in Dravet syndrome.

Dravet syndrome is currently considered as an developmental and epileptic encephalopathy and, recently, mandatory, alert, and exclusionary criteria have been proposed. Here, we describe three patients with Dravet syndrome with the typical early presentation including febrile and afebrile alternating hemiclonic seizures due to loss-of-function SCN1A variants. Subsequently, they developed episodes of febrile focal status epilepticus (SE) associated with hemiparesis and cerebral hemiatrophy with posterior focal seizures, as a consequence of Dravet syndrome. This sequence of events has been previously published in patients with Dravet syndrome and does not contradict the recent classification by the International League Against Epilepsy (ILAE). The ILAE guidance identifies "Focal neurological findings" as alert criteria and "MRI showing a causal focal lesion" as exclusionary criteria for making an initial diagnosis of Dravet syndrome at presentation. Our three patients would correspond to a severe phenotype, similar to the well-known presentation of generalized atrophy following prolonged status epilepticus. Common genetic findings in cases of diffuse and unilateral brain involvement may help explain these clinical presentations. Further genotype-phenotype studies may provide additional insights into this electroclinical behavior.

Probable 4-Repeat Tauopathy Criteria Predict Brain Amyloid Negativity, Distinct Clinical Features, and FDG-PET/MRI Neurodegeneneration Patterns in Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is associated with diverse underlying pathologies, including the four-repeat (4R)-tauopathies. The Movement Disorders Society (MDS) criteria for progressive supranuclear palsy (PSP) proposed the novel category "probable 4R-tauopathy" to address the phenotypic overlap between PSP and corticobasal degeneration (CBD). OBJECTIVES: To investigate the clinical ability of the MDS-PSP criteria for probable 4R-tauopathy in predicting a negative amyloid-PET in CBS. Additionally, this study aims to explore CBS patients classified as 4R-tauopathy concerning their clinical features and neuroimaging degeneration patterns. METHODS: Thirty-two patients with probable CBS were prospectively evaluated and split into those who fulfilled or did not fulfill the 4R-tauopathy criteria (CBS-4RT+ vs. CBS-4RT-). All patients underwent positron emission tomographies (PET) with [18 F]fluorodeoxyglucose and [11 C]Pittsburgh Compound-B (PIB) on a hybrid PET-MRI scanner to perform multimodal quantitative comparisons with a control group. RESULTS: Eleven patients were clinically classified as CBS-4RT+, and only one had a positive PIB-PET. The CBS-4RT+ classification had 92% specificity, 52% sensitivity, and 69% accuracy in predicting a negative PIB-PET. The CBS-4RT+ group presented with dysarthria and perseveration more often than the CBS-4RT- group. Moreover, the CBS-4RT+ group showed a prominent frontal hypometabolism extending to the supplementary motor area and striatum, and brain atrophy at the anterior cingulate and bilateral striata. CONCLUSIONS: The 4R-tauopathy criteria were highly specific in predicting a negative amyloid-PET in CBS. Patients classified as 4R-tauopathy presented distinct clinical aspects, as well as brain metabolism and atrophy patterns previously associated with tauopathies.

Acute exercise modulates Trim63 and Bmal1 in the skeletal muscle of IL-10 knockout mice.

The anti-inflammatory role of physical exercise is mediated by interleukin 10 (IL-10), and their release is possibly upregulated in response to IL-6. Previous studies demonstrated that mice lacking IL-6 (IL-6 KO mice) exhibited diminished exercise tolerance, and reduced strength. Rev-erbα, a transcriptional suppressor involved in circadian rhythm, has been discovered to inhibit the expression of genes linked to bodily functions, encompassing inflammation and metabolism. It also plays a significant role in skeletal muscle and exercise performance capacity. Given the potential association between Rev-erbα and the immune system and the fact that both pathways are modulated following acute aerobic exercise, we examined the physical performance of IL-10 KO mice and analyzed the modulation of the atrophy and Rev-erbα pathways in the muscle of wild type (WT) and IL-10 KO mice following one session of acute exercise. For each phenotype, WT and IL-10 KO were divided into two subgroups (Control and Exercise). The acute exercise session started at 6 m/min, followed by 3 m/min increments every 3 min until animal exhaustion. Two hours after the end of the exercise protocol, the gastrocnemius muscle was removed and prepared for the reverse transcription-quantitative polymerase chain reaction (RT-q-PCR) and immunoblotting technique. In summary, compared to WT, the IL-10 KO animals showed lower body weight and grip strength in the baseline. The IL-10 control group presented a lower protein content of BMAL1. After the exercise protocol, the IL-10 KO group had higher mRNA levels of Trim63 (atrophy signaling pathway) and lower mRNA levels of Clock and Bmal1 (Rev-erbα signaling pathway). This is the first study showing the relationship between Rev-erbα and atrophy in IL-10 KO mice. Also, we accessed a public database that analyzed the gastrocnemius of MuRF KO mice submitted to two processes of muscle atrophy, a denervation surgery and dexamethasone (Dexa) injections. Independently of knockout, the denervation demonstrated lower Nr1d1 levels. In conclusion, IL-10 seems to be a determinant in the Rev-erbα pathway and atrophy after acute exercise, with no modulation in the baseline state.