Screening for diminished ovarian reserve in Portugal: a cost-saving answer to shorten the fertility journey.

Aim: Assess the budget impact of nationwide screening for diminished ovarian reserve (OR), via anti-Müllerian hormone (AMH) levels, to the Portugal National Health System (NHS). Patients & methods: The clinical journey was determined using literature and the family planning decision-making process/response using survey results. A panel of four local clinicians validated all assumptions/inputs. Results: Screening for OR led to an expected savings of € 9.4 million for the NHS, driven by a 24% reduction in medically assisted reproduction (MAR) use. When needed, referral for MAR was earlier and more women used first-line versus second-line techniques. The model estimated a 12% decrease in failure. Conclusion: This model shows AMH screening may allow more informed decisions, leading to a shorter fertility journey, more efficient use of treatments, and substantial cost-savings for the NHS.

The migraine postdrome: Clinical characterization, influence of abortive treatment and impact in the quality of life.

OBJECTIVE: To determine the postdrome's prevalence and characterize its clinical manifestations, to assess the impact of these symptoms on the patients' activities of daily living, work activity and quality of life and to assess the factors that influence the postdrome's frequency and duration. METHODS: One hundred patients with migraine were screened about the occurrence of postdrome and its characteristics using a self-fulfilled questionnaire. RESULTS: Ninety-four patients reported between 1 and 23 postdrome symptoms (mean 8.0 ± 4.3 symptoms). The most reported symptoms were fatigue, difficulty with concentration and head discomfort. The frequency of the headache did not influence the frequency of the postdrome but correlated with the number of postdrome symptoms and the postdrome's duration. 82.8 % of patients reported an impact in quality of life. Most of the patients (77.4 %) did not report a difference in the duration of the postdrome when taking medication to relieve the migraine headache. Discomfort felt did not differ between patients prescribed with different abortive medication. Patients prescribed with NSAID reported more postdrome symptoms while patients prescribed with triptans identified a bigger impact in quality of life. CONCLUSION: Postdrome symptoms are frequent, diverse and cause significant disability. Abortive treatment directed to pain control is not efficient in postdrome symptoms. Understanding this phase may enhance our understanding of migraine and lead to better therapeutic approaches.

Disease burden associated with alpha-1 antitrypsin deficiency: systematic and structured literature reviews.

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder characterised by reduced levels of circulating alpha-1 antitrypsin and an increased risk of lung and liver disease. Recent reviews of AATD have focused on diagnosis, epidemiology and clinical management; comprehensive reviews examining disease burden are lacking. Therefore, we conducted literature reviews to investigate the AATD disease burden for patients, caregivers and healthcare systems. Embase, PubMed and Cochrane libraries were searched for AATD publications from database inception to June 2021, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Most published AATD studies were small and short in duration, with variations in populations, designs, measures and outcomes, complicating cross-study comparisons. AATD was associated with significant pulmonary and hepatic morbidity. COPD, emphysema and bronchiectasis were common lung morbidities, where smoking was a key risk factor. Fibrosis and steatosis were the most common liver complications reported in patients with a PiZ allele. Health status analyses suggested a poorer quality of life for AATD patients diagnosed with COPD versus those with non-AATD-associated COPD. The burden for caregivers included loss of personal time due to caring responsibilities, stress and anxiety. AATD was also associated with high direct medical costs and healthcare resource utilisation.

Sporadic Creutzfeldt-Jakob disease presenting as epilepsia partialis continua and non-ictal nystagmus.

BACKGROUND AND PURPOSE: Creutzfeldt-Jakob disease (CJD) is a rare form of rapidly progressive neurodegenerative disorder. Seizures are uncommon in the early stage of CJD, increasing diagnostic difficulty. METHODS: An autopsy-proven case of CJD presenting initially as an epilepsia partialis continua is reported, in which the initial workup was unremarkable. Retrospectively, the presence of nystagmus, which proved to be non-epileptic, pointed to a cerebellar lesion before a diagnosis of clinically probable CJD was made. RESULTS: A 70-year-old man presented with a 3-week history of intermittent rhythmic jerking tremors in his left limbs, interfering with his gait. Examination showed left body clonic movements. Electroencephalography revealed an ictal right centroparietal pattern of focal status epilepticus. Video-oculography revealed right-beating nystagmus (mean slow phase velocity [SPV] 3.4º/s) in the dark and left-beating nystagmus (SPV 2.6º/s) in the light, left-beating nystagmus after head shaking (SPV 4º/s) and during mastoid vibration (SPV 11º/s) and mildly hypoactive horizontal head impulses. Search for occult malignancy, serologies, cerebrospinal fluid analyses, anti-onconeural antigen, auto-immune panel and brain magnetic resonance imaging were unrevealing. Rapid neurological decline was observed. Three weeks later, cerebrospinal fluid was positive for 14.3.3 protein, electroencephalography showed generalized periodic sharp wave complexes and brain magnetic resonance imaging revealed diffusion restriction and T2/fluid-attenuated inversion recovery hyperintensities in the cerebellum, basal ganglia, thalamus and cortex. He died 1 month later. Neuropathological study confirmed the diagnosis of CJD. CONCLUSION: This case highlights that CJD should be considered in the differential diagnosis of new onset epilepsia partialis continua and that neuro-ophthalmological examination can be helpful in pointing to early asymmetric cerebellar involvement.

C-reactive protein as a predictor of mild cognitive impairment conversion into Alzheimer's disease dementia.

BACKGROUND AND AIMS: Increasing evidence suggests that inflammation plays an important role in brain aging and neurodegeneration. Pathological studies demonstrate the presence of C-reactive protein (CRP) in the senile plaques and neurofibrillary tangles in Alzheimer's disease (AD) brain tissue suggesting that CRP may play a role in its neuropathological processes. Some findings suggest that midlife elevations of serum CRP are a risk factor for AD. However, others found lower CRP levels in mild or moderate AD than in controls, suggesting that CRP levels could be different in different stages of disease. We aimed to assess the role of CRP as a predictor of Mild cognitive impairment (MCI) conversion into AD dementia. METHODS: We retrospectively reviewed the cohort of MCI patients followed at the Dementia Clinic, Neurology Department of University Hospital of Coimbra. We collected demographical, neuropsychological, genetic and laboratorial variables (including serum CRP measurements at the time of baseline laboratory tests). A Cox regression model was performed adjusted for the collected variables preconsidered to be predictors of dementia and the variable being studied (CRP) to assess for independent predictors of conversion. RESULTS: We included 130 patients, 58.5% female, with a mean age of onset of 65.5 ± 9.1 years and age at first assessment of 69.3 ± 8.5 years. The mean CRP was 0.33 ± 0.58 mg/dl. At follow-up (mean, 36.9 ± 27.0 months) 42.3% of MCI patients converted to dementia. Lower CSF Aß42 (HR = 0.999, 95%CI = [0.997, 1.000], p = 0.015), lower MMSE score (HR = 0.864, 95%CI = [0.510, 1.595], p = 0.008) and lower CRP quartile (HR = 0.597, 95%CI = [0.435, 0.819], p = 0.001) were independent predictors of conversion. CONCLUSION: CRP may add information of risk of conversion in MCI patients. Patients with lower CRP levels appear to have a more rapid conversion to AD dementia.

Anti-NMDAR Encephalitis Following Herpes Simplex Virus Encephalitis: 2 Cases From Portugal.

Herpes simplex virus encephalitis (HSVE) usually presents as a monophasic disease. Symptomatic HSVE relapsing with seizures, encephalopathy, or involuntary movements associated with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis have been recently reported. We report 2 cases of adult post-HSVE anti-NMDAR encephalitis from Portugal. Two female patients aged 50 years and 30 years were diagnosed with herpes simplex virus type 2 and type 1 encephalitis, respectively. After the initial improvement with specific treatment and despite virologic negativization, both patients suffered clinical, electroencephalographic, and imaging deterioration. The autoimmune encephalitis hypothesis was confirmed with the demonstration of anti-NMDAR antibodies in both cerebrospinal fluid and serum. Both responded to human immunoglobulin and methylprednisolone, with progressive gain of autonomy along the follow-up period. Thymectomy for thymic hyperplasia diagnosed during follow-up was performed in 1 patient. Although being rare, post-HSVE anti-NMDAR encephalitis should be considered in all cases of symptomatic recrudescence after HSVE, since adequate immune-modulating treatment improves the outcome. The role of thyme hyperplasia in autoimmune encephalitis pathogenesis needs better understanding.

Addition of the Aß42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer's disease dementia in mild cognitive impairment.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer's disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF Aß42 concentration to the level of total amyloid beta (Aß), using the Aß42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia. Therefore, we evaluated whether the Aß42/40 ratio would improve MCI categorization and more accurately predict progression to AD. METHODS: Our baseline population consisted of 197 MCI patients, of which 144 had a follow-up ≥ 2 years, and comprised the longitudinal study group. To establish our own CSF Aß42/40 ratio reference value, a group of 168 AD-dementia patients and 66 neurological controls was also included. CSF biomarker-based classification was operationalized according to the framework of the National Institute of Aging-Alzheimer Association criteria for MCI. RESULTS: When using the core CSF biomarkers (Aß42, total Tau and phosphorylated Tau), 30% of the patients fell into the high-AD-likelihood (HL) group (both amyloid and neurodegeneration markers positive), 30% into the low-AD-likelihood group (all biomarkers negative), 28% into the suspected non-Alzheimer pathophysiology (SNAP) group (only neurodegeneration markers positive) and 12% into the isolated amyloid pathology group (only amyloid-positive). Replacing Aß42 by the Aß42/40 ratio resulted in a significant increase in the percentage of patients with amyloidosis (42-59%) and in the proportion of interpretable biological profiles (61-75%), due to a reduction by half in the number of SNAP cases and an increase in the proportion of the HL subgroup. Survival analysis showed that risk of progression to AD was highest in the HL group, and increased when the Aß42/40 ratio, instead of Aß42, combined with total Tau and phosphorylated Tau was used for biomarker-based categorization. CONCLUSIONS: Our results confirm the usefulness of the CSF Aß42/40 ratio in the interpretation of CSF biomarker profiles in MCI patients, by increasing the proportion of conclusive profiles and enhancing their predictive value for underlying AD.

Coloretal cancer in pregnant women / Cancro colorectal na mulher grávida

Abstract Background Colorectal cancer in pregnancy is a rare pathology with limited high-grade evidence available for guidance. The diagnosis of CRC in pregnant women is usually delayed, and once diagnosis is made, challenges exist as treatment options may be limited. Objective The study aims to highlight the importance of early investigation of symptomatic patients during pregnancy, as well as to update treatment and prognosis in CRC. Methods A literature search in PubMed database, including articles from 2006 to 2016 and cross-research articles with the initial research. Results Pregnancy can limit and contraindicate the utilization of standard diagnostic and therapeutic tools, which in particular can hamper the liberal use of colonoscopy and CT. Physical evaluation and abdominal US are first recommended; besides, MRI or CT may be used, only in indicated cases. Surgery is the main stay of treatment but radiotherapy and chemotherapy have significant role in posterior management of tumour. Conclusions Many studies are needed in order to achieve development in CRC pathogenesis during pregnancy as well as in treatment outcomes. The potential curative treatment of the disease should be the main aim of treatment when considering CRC in pregnancy. However, it is crucial to adapt the treatment to each patient, taking into account conscious decision on pregnancy further management.

Resumo Introdução O cancro colorretal na gravidez é uma patologia rara, com limitada evidência científica para orientação terapêutica. O diagnóstico de cancro coloretal em mulheres grávidas é tardio e, quando o diagnóstico é feito, as opções de tratamento podem ser limitadas. Objetivo O objetivo deste estudo é ressalvar a importância da investigação precoce de pacientes sintomáticas durante a gravidez, assim como avaliar os atuais métodos de tratamento e prognóstico no CCR. Métodos A pesquisa bibliográfica foi realizada na base de dados PubMed, incluindo artigos a partir de 2006 até 2016, assim como artigos de pesquisa cruzada com os artigos iniciais. Resultados A gravidez pode limitar e contra-indicar a utilização de ferramentas de diagnóstico e terapêuticas convencionais, assim como dificultar o uso indiscriminado de colonoscopia e tomografia computadorizada. A avaliação física e a ecografia abdominal são a primeira linha para diagnóstico. No entanto, em casos selecionados, a ressonância magnética ou a tomografia computadorizada também podem ser usadas. A cirurgia é o gold-standard mas a radioterapia e a quimioterapia assumem um papel cada vez mais relevante no tratamento multidisciplinar destes tumores. Discussão Como os sintomas abdominais são comuns na gravidez e cancro coloretal pode simulá-los, o diagnóstico diferencial entre estas duas patologias é crucial, já que intervenções precoces podem ser curativas. Após diagnóstico, o seguimento das grávidas deve ser individualizado, dependendo de vários fatores. Porém, já que atualmente o tratamento do cancro é possível na gravidez, a probabilidade de sobrevivência da paciente não deve ser diminuída devido ao diagnóstico tardio. Conclusões Mais estudos são necessários para saber mais acerca da patogénese do cancro coloretal na gravidez, assim como os resultados após tratamento. O potencial objetivo é o tratamento oncológico do cancro coloretal. No entanto, é crucial adaptar o tratamento a cada paciente, tendo em conta a sua decisão consciente acerca da continuação da gravidez.

Portuguese version of Wechsler Memory Scale-3rd edition's utility with demented elderly adults.

The purpose of this study is to analyze the utility of the Portuguese version of the Wechsler Memory Scale-3rd edition (WMS-III) with demented elderly people, namely its capacity to detect and discriminate between subcortical vascular dementia (SVD) and Alzheimer's disease (AD). We assessed early demented patients (SVD = 16; AD = 36) aged 65 or older who were compared to a control group (n = 40). Both clinical groups were adequately matched in terms of disease severity, overall cognitive functioning, depressive symptomatology, and pre-morbid intelligence. Between-group's differences were evaluated using the Quade's rank analysis of covariance. We also computed indexes and subtests optimal cut-off scores, and the corresponding sensitivity, specificity, and positive and negative predictive values, which were able to successfully discriminate between patients and healthy subjects. The SVD patients had a better overall memory performance than AD patients on the majority of the indexes and the delayed condition subtests of the WMS-III. The AD patients only showed a better performance on digit span subtest. Several measures discriminated patients from healthy subjects. This study suggests some recommendations for the diagnostic accuracy of the Portuguese version of WMS-III in dementia and about differential diagnosis between SVD and AD.

The Portuguese version of Addenbrooke's Cognitive Examination-Revised (ACE-R) in the diagnosis of subcortical vascular dementia and Alzheimer's disease.

The aim of this study was to investigate the accuracy of the Portuguese version of Addenbrooke's Cognitive Examination-Revised (ACE-R) in detecting and differentiating early stage subcortical vascular dementia (SVD) from early stage Alzheimer's disease (AD). Ninety-two subjects (18 SVD patients, 36 AD patients, and 38 healthy controls) were assessed using the ACE-R. Between-group's differences were evaluated using the Quade's rank analysis of covariance. The diagnostic accuracy and discriminatory ability of the ACE-R were examined via receiver operating characteristic (ROC) analysis. The ACE-R was able to successfully discriminate between patients and healthy subjects. The mean ACE-R total scores differed between SVD and AD patients; there were also significant differences in attention and orientation and in memory measures between the groups. An optimal cut-off of 72/73 was found for the detection of AD (sensitivity: 97%; specificity: 92%) and SVD (sensitivity: 100%; specificity: 92%).

[Healthcare associated infection: emerging problem in a neurology department]. / Infecção associada aos cuidados de saúde: problema emergente num serviço de neurologia.

BACKGROUND: Healthcare-associated infection (HAI) is, nowadays, a serious problem, contributing a lot to the burden of the hospital stays. Its impact is really huge and the study of these matters is taking a growing interest. AIMS: To compare, in terms of HAI, the current Neurology Department (localized inside the building of Hospital Geral) and the oldest one, which was far away from the institutional campus. To identify difficulties regarding the management of HAI, trying to propose measures for quality improvement. METHODS: We revised the clinical files of the patients with HAI documented by culture, on a homologue period of 6 months. Variables like more frequently isolated microorganisms, antibiotics sensibilities, patients' comorbidities, treatment adequacy and duration of hospitalization were analyzed. RESULTS: In the oldest Department, 23 patients were identified, 8 men (mean +/- 2SD: 80.4 +/- 9.04 years old) and 15 women (77.3 +/- 21.28 years old), with positive microbiological studies (51). Ischemic stroke caused 73.9% of these hospitalizations. Escherichia coli - EC - (27%), methicillin-resistant Staphylococcus aureus - MRSA - (22%) and Klebsiella pneumoniae - KP - (10%) were the most frequently identified microorganisms in the biological samples studied (sputum, urine, blood, urethral exudate and eschar). Amoxicillin/clavulanic acid was the most empirically used antibiotic (only effective on 37% of the cases, according to the sensibility tests). Hospitalizations had an average of 22 days and 1.3 antibiotics per patient were used. At discharge, Rankin had a mode of 5. In the current Department, 46 patients were studied, 22 men (76.4 +/- 22.6 years old) and 24 women (74.1 +/- 32.6 years old), having 119 positive cultures. Again, ischemic stroke caused the majority of the admissions (52.2%). MRSA (26%), Pseudomonas aeruginosa - PA - (17%) and EC (17%) were the most prevalent pathogens (the same biological products were studied, plus lingual exudates and central venous catheter tips). Ciprofloxacin was the most used antibiotic (suitable on 75% of the cases). Internments had an average of 24.3 days and, this time, 2.5 antibiotics were used per patient, by mean. At discharge, Rankin evaluation had again a mode of 5. DISCUSSION: Despite the taken measures and change in facilities, HAI had really increased in the Neurology Department. Since human resources are the same, we think are important, as possible aggravating conditions, space restriction and ward sharing with patients of other medical specialities, as it happens in the current Department. CONCLUSIONS: More aggressive pathogens require a rapid and comprehensive intervention, in order to minimize its impact on daily clinical practice and in the management of hospital stays.