A doença de Parkinson é a segunda doença neurodegenerativa mais comum, tendo sido documentado um aumento significativo da sua prevalência nas últimas três décadas. A fisiopatologia da doença assenta numa interação genética-ambiente, estimando-se que cerca de 5% – 10% dos casos tenham causa genética monogénica. O diagnóstico é clínico, apoiado por investigação complementar adequada. Não dispomos ainda de uma forma de diagnosticar com certeza a doença de Parkinson in vivo, à exceção de testes genéticos em circunstâncias específicas, cuja utilidade é limitada a uma minoria de casos. Recentemente foram propostos novos critérios de diagnóstico, com o objetivo de melhorar a acuidade diagnóstica, com ênfase nas características que apontam para outras causas de parkinsonismo. As opções terapêuticas atualmente disponíveis são clinicamente úteis, pois têm a capacidade de melhorar os sintomas da doença e a qualidade de vida dos doentes. Após a introdução da levodopa, a estimulação cerebral profunda surgiu, mais recentemente, como a segunda intervenção terapêutica com importante impacto sintomático no tratamento desta doença. Os sintomas não motores e as complicações motoras são responsáveis por uma parte considerável da incapacidade na doença de Parkinson, pelo que devem ser identificados e tratados. A investigação científica atual foca-se na identificação de potenciais biomarcadores da doença, que permitam alcançar um diagnóstico certeiro e atempado, e na criação de terapêuticas mais eficazes, de modo a preencher as necessidades clínicas atualmente não satisfeitas. Este artigo apresenta uma revisão atualizada sobre a doença de Parkinson, guiando o leitor através dos conceitos mais atualizados nesta temática, de forma a permitir a sua aplicação na prática clínica diária.

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.

Background The literature on predictors of persistent postural-perceptual dizziness (PPPD) following peripheral vestibular insults has not been systematically reviewed. Methods We systematically reviewed studies on predictors of PPPD and its four predecessors (phobic postural vertigo, space-motion discomfort, chronic subjective dizziness and visual vertigo). Investigations focused on new onset chronic dizziness following peripheral vestibular insults, with a minimum follow-up of 3 months. Precipitating events, promoting factors, initial symptoms, physical and psychological comorbidities and results of vestibular testing and neuroimaging were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results We identified 13 studies examining predictors of PPPD or PPPD-like chronic dizziness. Anxiety following vestibular injury, dependent personality traits, autonomic arousal and increased body vigilance following precipitating events and visual dependence, but not the severity of initial or subsequent structural vestibular deficits or compensation status, were the most important predictors of chronic dizziness. Disease-related abnormalities of the otolithic organs and semi-circular canals and age-related brain changes seem to be important only in a minority of patients. Data on pre-existing anxiety were mixed. Conclusions After acute vestibular events, psychological and behavioural responses and brain maladaptation are the most likely predictors of PPPD, rather than the severity of changes on vestibular testing. Age-related brain changes appear to have a smaller role and require further study. Premorbid psychiatric comorbidities, other than dependent personality traits, are not relevant for the development of PPPD.

Despite all the knowledge already gathered, the picture of somatic genetic changes in colorectal tumorigenesis is far from complete. Recently, germline and somatic mutations in the exonuclease domain of polymerase epsilon, catalytic subunit (POLE) gene have been reported in a small subset of microsatellite‐stable and hypermutated colorectal carcinomas (CRCs), affecting the proofreading activity of the enzyme and leading to misincorporation of bases during DNA replication. To evaluate the role of POLE mutations in colorectal carcinogenesis, namely in advanced CRC, we searched for somatic mutations by Sanger sequencing in tumor DNA samples from 307 cases. Microsatellite instability and mutation analyses of a panel of oncogenes were performed in the tumors harboring POLE mutations. Three heterozygous mutations were found in two tumors, the c.857C>G, p.Pro286Arg, the c.901G>A, p.Asp301Asn, and the c.1376C>T, p.Ser459Phe. Of the POLE‐mutated CRCs, one tumor was microsatellite‐stable and the other had low microsatellite instability, whereas KRAS and PIK3CA mutations were found in one tumor each. We conclude that POLE somatic mutations exist but are rare in advanced CRC, with further larger studies being necessary to evaluate its biological and clinical implications.

Functional cognitive disorder (FCD) accounts for around a third of patients attending specialized memory clinics. It is also overrepresented in patients with other functional and somatic diagnoses. So far, no long-term diagnostic validity studies were conducted, and a positive diagnostic profile is yet to be identified. We aimed to review the literature on diagnostic signs and symptoms that allow for a discrimination between FCD and neurodegeneration. Systematic review of Ovid-Medline®, Embase and PsycINFO databases. Relevant clinical features were extracted including demographics, symptom history, comorbidities, language and interaction profiles and cognitive assessments. Studies with quantifiable diagnostic accuracy data were included in a diagnostic meta-analysis. Thirty studies (N = 8602) were included. FCD patients were younger, more educated, and more likely to have a family history of older onset dementia, abrupt symptom onset, and higher rates of anxiety, depression and sleep disturbance. Promising language profiles include longer duration of spoken answer, elaborated examples of memory failures, ability to answer compound and personal questions, and demonstration of working memory during interaction. The pooled analysis of clinical accuracy of different signs revealed that attending alone and bringing a handwritten list of problems particularly increase the odds of a FCD diagnosis. Current evidence from neuropsychometric studies in FCD is scarce. Our systematic review reinforces that positive signs contribute for an early differentiation between FCD and neurodegeneration in patients presenting with memory complaints. It is the first to attain quantitative value to clinical observations. These results will inform future diagnostic decision tools and intervention testing.