Epilepsy and sleep disorders improve in adolescents and adults with Angelman syndrome: A multicenter study on 46 patients.

OBJECTIVE: Actual knowledge on evolution of Angelman syndrome (AS) relies on questionnaire-based cohort studies, phone interviews, or small retrospective cohort studies focused on specific clinical-genetic features. These reports provide conflicting results. The aim of this study was to assess the long-term outcome of epilepsy, sleep disorders, and EEG in a vast series of AS subjects. METHODS: We collected patients with genetically confirmed AS, aged ≥14years, followed in three tertiary epilepsy Centers or attending the meetings of the Italian Organization for AS (OrSA). Retrospective clinical and EEG data were retrieved from hospital archives or family documents. At index evaluation (IE) (last visit at tertiary Centers or single visit during OrSA meetings), caregivers were interviewed about anamnestic data and filled questionnaires on sleep disorders and daily-living skills. Patients underwent general and neurologic evaluation, and video-EEG recordings. All available EEGs were analyzed to compare evolution of spike-wave index (SWI) over the years. RESULTS: Forty-six subjects aged 14-45years were included: 24 from tertiary Centers, 22 from OrSA meetings. During childhood, 42/46 (91.3%) had seizures, which improved over the years in all subjects. Among patients with epilepsy, 27(64%) became seizure-free at a median age of 10years and 4 remained seizure-free even after antiepileptic withdrawal. During childhood, 39/46 (84.8%) had sleep disorders, which improved in 27/39 (69%) over the years. At IE, daily-living skills corresponded to age≤1.6years in 29/46 (63%). Electroencephalogram showed typical AS patterns in 35/46 (76.1%). In EEGs recorded from 10 patients, SWI was not significantly different between infancy/childhood and adolescence/adulthood. CONCLUSION: Improvement of epilepsy or sleep disorders should not disregard the clinical suspicion of AS in adolescent or adult patients with suggestive features. Drug withdrawal might be considered in the management of epilepsy despite the persistence of epileptiform abnormalities.

Positivity to p-ANCA in patients with status epilepticus.

BACKGROUND: Status epilepticus (SE) may occur in the setting of several internal or neurologic diseases. Anti-neutrophilic cytoplasmic antibodies (ANCA) are a group of Ig that may be observed in patients with different autoimmune disorders but are particularly associated with systemic vasculitis named ANCA-associated-vasculities (AAV). We herein report 3 patients with SE and positivity to p-ANCA. CASE PRESENTATION: One patient had a catastrophic evolution and died 5 months after disease onset. The other two patients had a good outcome and remained seizure-free at 30 months and 5 years of follow-up respectively. CONCLUSION: This report highlights the importance of considering ANCA dosage in patients with SE of unclear origin.

Randomized controlled trial comparing highly purified (HP-hCG) and recombinant hCG (r-hCG) for triggering ovulation in ART.

BACKGROUND: A randomized controlled trial (RCT) comparing highly purified human Choriogonadotrophin (HP-hCG) and recombinant hCG (r-hCG) both administered subcutaneously for triggering ovulation in controlled ovarian stimulation (COS) for Assisted Reproductive Technology (ART). METHODS: Multi-centre (n = 4), prospective, controlled, randomized, non-inferiority, parallel group, investigator blind design, including 147 patients. The trial was registered with www.clinicaltrials.gov, using the identifier: NCT00335569. The primary endpoint is the number of oocytes retrieved, while the secondary endpoints include embryo implantation, pregnancy and delivery rates as well as safety parameters. RESULTS: The number of retrieved oocytes was not inferior when HP-hCG was used as compared to r-hCG: the mean number was 13.3 (6.8) in HP-hCG and 12.5 (5.8) in the r-hCG group (p = 0.49) with a 95% CI (-1.34, 2.77). Regarding the secondary outcomes, there were also no differences in fertilization rate at 57.3% (467/815) vs. 61.3% (482/787) (p = 0.11), the number of embryos available for transfer and cryopreservation (2PN stage) and implantation, pregnancy and delivery rates. Furthermore, there were no differences in the number and type of adverse events reported. HP-hCG was therefore not inferior to r-hCG. CONCLUSIONS: HP-hCG and r-hCG are equally efficient and safe for triggering ovulation in ART and, both being administered subcutaneously, equally practical and well tolerated by patients.

COVID-19 Neuromuscular Involvement in Post-Acute Rehabilitation.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with muscle and nerve injuries as a consequence of prolonged critical illness or the infection itself. In this study, we evaluated neuromuscular involvement in patients who underwent post-acute intensive rehabilitation after COVID-19. METHODS: Clinical and neurophysiological evaluations, including nerve conduction studies and electromyography, were performed on 21 consecutive patients admitted for rehabilitation after COVID-19. RESULTS: Clinical signs suggesting muscle or nerve involvement (weakness, reduced deep tendon reflexes, impaired sensitivity, abnormal gait) were found in 19 patients. Neurophysiological examinations confirmed neuromuscular involvement in 17 patients: a likely association of critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) was found in 5 patients; CIM alone was found in 4 patients; axonal sensory-motor polyneuropathy was found in 4 patients (CIP in 2 patients, metabolic polyneuropathy in 2 patients); Guillain-Barré syndrome was found in 2 patients (classical demyelinating sensory-motor polyneuropathy and acute motor axonal neuropathy, respectively); peroneal nerve injury was found in 1 patient; and pre-existing L4 radiculopathy was found in 1 patient. CONCLUSIONS: Neuromuscular involvement is a very common finding among patients admitted for rehabilitation after COVID-19, and proper investigation should be conducted when muscle or nerve injury is suspected for adequate rehabilitative strategy planning.

Poor reliability of vaginal and endocervical cultures for evaluating microbiology of endometrial cavity in women with chronic endometritis.

BACKGROUND: Chronic endometritis (CE) is a subtle pathology causing infertility and abnormal uterine bleeding. We evaluated the reliability of vaginal and cervical cultures for detecting infectious agents at the endometrial level. METHODS: In a prospective diagnostic study, 181 women diagnosed with CE and 100 controls underwent vaginal, endocervical and endometrial sampling. Cultures for common bacteria, Neisseria gonorrhoeae, yeast and Ureaplasma urealyticum and PCR for Chlamydia trachomatis were performed. RESULTS: The prevalent infectious agents at the endometrial level were common bacteria(59.7% of cases); U. urealyticum was detected in 11.0% and C. trachomatis in only 2.8%. The concordance rate between endocervical and endometrial specimens for common bacteria was 48.3%; 100% for C. trachomatis and 58.3% for U. urealyticum. The concordance rate between vaginal and endometrial cultures for common bacteria was 50.2%, only 16.7% for C. trachomatis and 48.8% for U. urealyticum. For common bacteria both vaginal and cervical cultures showed low sensitivities of 0.30 and 0.19, respectively. CONCLUSION: Common bacteria and U. urealyticum were the prevalent infectious agents in the uterine cavity of women diagnosed with CE. Both vaginal and endocervical cultures had low concordance with endometrial cultures. Only C. trachomatis test at cervical level had high concordance with endometrial findings.

Choline-PET/CT in the Differential Diagnosis Between Cystic Glioblastoma and Intraparenchymal Hemorrhage.

OBJECTIVE: Glioblastoma multiforme (GBM) represents the most common and malignant glioma, accounting for 45%-50% of all gliomas. The median survival time for patients with glioblastoma is only 12-15 months after surgical, chemioterapic and radiotherapic treatment; a correct diagnosis is naturally fundamental to establish a rapid and correct therapy. Non-invasive imaging plays a pivotal role in each phase of the diagnostic workup of patients with suspected for diagnosis. The aim of this case report was to describe the potential clinical impact of 18F-fluorocholine (FCH) PET/CT in the assessment of a cystic GBM mimicking a spontaneous hemorrhage. METHODS: a 57 years-old male with intraparenchymal hemorrhage at CT imaging initially in reduction ad serial imaging and suspected right fronto-temporo-parietal lesion at MRI underwent dynamic and static (60' after tracer injection) FCH PET/CT of the brain. RESULTS: FCH PET/CT showed rapid tracer uptake after few second from injection at dynamic acquisition and consequent incremental mild uptake at static imaging after 60 minutes at the level of oval formation in the right cerebral hemisphere characterized by annular and peripheral high metabolic activity. The central region of the lesion was characterized by the absence 18F-FCH uptake most likely due to blood component. The patient underwent surgery for tumor removal; the histopathological examination confirmed the suspect of GBM. Chemo-radiotherapic adjuvant protocol according to Stupp protocol was therefore administrated; to date the patient is alive without any progression disease at 5 months from treatment. CONCLUSION: In this case report FCH PET/CT represented the final diagnostic technique to confirm the suspicious of a cystic GBM. Our case demonstrated the potential role of 18F-FCH PET/CT for discrimination of higher proliferation area over intraparenchymal hemorrhage, supporting the potential use of this imaging biomarker in surgical or radiosurgical approach. Obviously, further prospective studies are needed to confirm this role and to exactly define possible routinely applications.

Epilepsy associated with Leukoaraiosis mainly affects temporal lobe: a casual or causal relationship?

OBJECTIVE: To compare anatomo-electro-clinical findings between patients with epilepsy associated with leukoaraiosis only (EAL) and patients with a well-defined vascular lesion, i.e. post-stroke epilepsy (PSE). METHODS: Two hundred eighty-three subjects with epilepsy and cerebrovascular disease, consecutively seen in our epilepsy centres from January 2000 to March 2014, were retrospectively considered. Inclusion criteria were: history of one or more unprovoked seizures and MRI evidence of one or more vascular lesions. Exclusion criteria were: inadequate neuroimaging data, coexistence of nonvascular lesions, and psychogenic seizures. Subjects were divided in two groups: PSE and EAL, based onclinical and MRI findings. Epileptogenic focus was identified according to ictal semiology and EEG findings. In PSE group, coherence between the vascular lesion(s) and epileptogenic focus was scored as likely or unlikely. RESULTS: One hundred seventeen subjects were included: 58 had PSE, 59 EAL. Coherence was identified as likely in 38 (95%) and unlikely in 2 (5%). At univariate analysis, abnormal EEG and frontal localization were associated with a lower EAL probability [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.15-0.87, p=0.02 and OR 0.12, 95% CI 0.04-0.37, p<0.001, respectively], while temporal localization was associated with a higher EAL probability (OR 4.0, 95% CI 1.8-9.0, p<0.001). Multivariate confirmed these associations. CONCLUSIONS: While in PSE epileptogenic focus is coherent with the vascular lesions, in EAL temporal lobe epilepsy predominates. In EAL, causal relationship between vascular lesions and epilepsy is not straightforward, and the role of adjunctive factors needs to be elucidated.

Fertility preservation in cancer patients. Review of the French speaking part of Switzerland and recommendations for different situations.

Due to constant progress in oncology, survival rates of patients (children and adults) with cancer are increasing. Consequently, the reproductive future of young cancer patients needs to be addressed carefully. Fertility preservation techniques are available and issues such as the time available for fertility treatments, patients' age, presence of a partner and patients' personal wishes have to be considered. In Switzerland, a first therapeutic network (Réseau Romand de Cancer et Fertilité), was created in the French speaking part of Switzerland in 2006. Since 2010, a global Swiss network (FertiSave) has been created. The goal of these networks is to maximise the safety and efficacy of fertility preservation options offered to cancer patients without compromising their oncological prognosis. Patients' needs have to be identified, the therapeutic options evaluated rapidly and the optimal treatment promptly implemented in these urgent situations. This article reviews the fertility preservation options currently available and makes recommendations for different specific cancer situations, consistent with the latest scientific evidence and in general agreement with international recommendations.

Fertility and cancer: psychological support in young women who contemplate emergency assisted reproductive technologies (ART) prior to chemo- and/or radiation-therapy.

PRINCIPLES: Women of reproductive age with cancer fear for their childbearing potential as a result of the cancer itself and chemo- and/or radiation-therapy. METHODS: Starting in 2006, a dedicated task force was set up at Lausanne University Hospital (CHUV) to handle all cancer and fertility issues and, in certain cases, offer access to emergency assisted reproductive technologies (ART) to preserve further childbearing options. Help provided by the task force was offered within a multidisciplinary framework encompassing psychological counselling offered to each patient or couple. RESULTS: We report here the salient points of the experience gained through dedicated psychological counselling offered to cancer patients concerned about their future fecundity. This was done with the intention of underscoring the most clinically relevant lessons learned through our experience at CHUV. CONCLUSIONS: The specific 'cancer and fertility' counselling instituted at CHUV offers support for young women or couples confronted with stressful cancer and fertility issues. This type of specific counselling, the resource counselling, appears to be a particularly appropriate tool for patients abruptly involved in difficult decision-making processes under time constraints and thus extremely vulnerable. The personal feedbacks from the patients also confirm the importance of offering specific counselling and timely psychological support of the type reported here to all women of reproductive age before starting chemo- and/or radiation-therapy.

Preimplantation genetic diagnosis (PGD) for HLA typing: bases for setting up an open international collaboration when PGD is not available.

In severe forms of Diamond-Blackfan anemia, preimplantation genetic diagnosis (PGD) of histocompatibility leukocyte antigen-compatible embryos for enabling the next sibling in the family to be a stem-cell transplantation donor constitutes the sole lasting cure capable of terminating the enduring need for iterative transfusions. We report here an open collaboration between two renowned institutions to provide a family desiring this treatment even though they resided where the preimplantation genetic diagnosis procedure is banned.

Outlook: Roles of FSH and LH during the follicular phase: insight into natural cycle IVF.

A mounting interest in natural cycle IVF has challenged the medical community to better understand the mechanisms controlling the follicular phase and ovulation in particular, in an effort to optimize this procedure and its outcome. For practical reasons, the advancement of the follicular phase in the menstrual cycle is commonly timed according to the onset of last menses. However, this precludes knowing when the follicular phase truly begins and hampers the possibility of optimizing timing of late follicular-phase events, notably, the triggering of ovulation. Clinicians, therefore, use surrogate markers of follicular maturation, such as oestrogen production and follicular size. Because it is impossible to identify the low-amplitude intercycle basal FSH signal, efforts have reverted toward controlling when it takes place, either with exogenous oestrogen or with oral contraceptives. In the late follicular phase, the occurrence of LH surge results from a balance between the opposite effects of rising oestrogen concentrations, which favour the LH surge, and the opposing effects mediated by the gonadotrophin surge-attenuating factor, a peptide of ovarian origin. This review looks into the mechanisms that control these two hinges of the follicular phase, the basal FSH signal and LH surge, in the context of optimizing natural cycle IVF.

Long-term effects of tibolone on circulating levels of vascular cell adhesion molecules and E-selectin in postmenopausal women.

OBJECTIVE: Adherence of lymphocytes and monocytes to cell adhesion molecules (vascular cell adhesion molecules [VCAMs]) expressed by activated endothelial cells is the first step in the development of atherosclerotic disease. It is known that administration of tibolone for 8 weeks reduces serum levels of VCAMs in postmenopausal women. We evaluated the effects of the administration of tibolone in postmenopausal women for 1 year. DESIGN: Randomized, placebo-controlled, crossover trial. SETTING: Healthy volunteers in an academic environment. PATIENT(S): Thirty-six healthy women in postmenopause since 1-4 years. INTERVENTION(S): Group A received 2.5 mg/d of tibolone and group B received placebo for 12 months; treatment was subsequently crossed over for 1 month. MAIN OUTCOME MEASURE(S): Serum concentrations of VCAM-1, intercellular adhesion molecule-1 (ICAM-1), and E-selectin were evaluated at baseline and at 6, 12, and 13 months. RESULT(S): Baseline concentration of VCAM-1, ICAM-1, and E-selectin were similar in both groups. At months 6 and 12, mean concentrations of VCAM-1, ICAM-1, and E-selectin decreased significantly in group A but not in group B. At month 13, levels returned to baseline in group A, whereas they decreased significantly in group B. CONCLUSION(S): Tibolone causes a rapid and sustained decrease in circulating levels of VCAMs; the effect is lost soon after stopping the treatment. Tibolone induces favorable changes in endothelial function and may exert a direct cardiovascular protective effect in postmenopausal women.

Endometrial effects, bleeding control, and compliance with a new postmenopausal hormone therapy regimen based on transdermal estradiol gel and every-other-day vaginal progesterone in capsules: a 3-year pilot study.

In a 3-year prospective study, 30 postmenopausal women received transdermal E2 gel and every-other-day vaginal P in capsules. At study completion, endometrial thickness was significantly reduced as compared with baseline (2.7 +/- 0.5 vs. 3.4 +/- 0.9 mm), endometrial biopsy showed endometrial atrophy in all cases, and amenorrhea was achieved in 92.6% of cycles, while excellent patient satisfaction was achieved.