Oral and intestinal dysbiosis in Parkinson's disease.

The suspicion of an origin of Parkinson's disease (PD) at the periphery of the body and the involvement of environmental risk factors in the pathogenesis of PD have directed the attention of the scientific community towards the microbiota. The microbiota represents all the microorganisms residing both in and on a host. It plays an essential role in the physiological functioning of the host. In this article, we review the dysbiosis repeatedly demonstrated in PD and how it influences PD symptoms. Dysbiosis is associated with both motor and non-motor PD symptoms. In animal models, dysbiosis only promotes symptoms in individuals genetically susceptible to Parkinson's disease, suggesting that dysbiosis is a risk factor but not a cause of Parkinson's disease. We also review how dysbiosis contributes to the pathophysiology of PD. Dysbiosis induces numerous and complex metabolic changes, resulting in increased intestinal permeability, local and systemic inflammation, production of bacterial amyloid proteins that promote α-synuclein aggregation, as well as a decrease in short-chain fatty acid-producing bacteria that have anti-inflammatory and neuroprotective potential. In addition, we review how dysbiosis decreases the efficacy of dopaminergic treatments. We then discuss the interest of dysbiosis analysis as a biomarker of Parkinson's disease. Finally, we give an overview of how interventions modulating the gut microbiota such as dietary interventions, pro-biotics, intestinal decontamination and fecal microbiota transplantation could influence the course of PD

Multi-centre classification of functional neurological disorders based on resting-state functional connectivity.

BACKGROUND Patients suffering from functional neurological disorder (FND) experience disabling neurological symptoms not caused by an underlying classical neurological disease (such as stroke or multiple sclerosis). The diagnosis is made based on reliable positive clinical signs, but clinicians often require additional time- and cost consuming medical tests and examinations. Resting-state functional connectivity (RS FC) showed its potential as an imaging-based adjunctive biomarker to help distinguish patients from healthy controls and could represent a "rule-in" procedure to assist in the diagnostic process. However, the use of RS FC depends on its applicability in a multi-centre setting, which is particularly susceptible to inter-scanner variability. The aim of this study was to test the robustness of a classification approach based on RS FC in a multi-centre setting. METHODS This study aimed to distinguish 86 FND patients from 86 healthy controls acquired in four different centres using a multivariate machine learning approach based on whole-brain resting-state functional connectivity. First, previously published results were replicated in each centre individually (intra-centre cross-validation) and its robustness across inter-scanner variability was assessed by pooling all the data (pooled cross-validation). Second, we evaluated the generalizability of the method by using data from each centre once as a test set, and the data from the remaining centres as a training set (inter-centre cross-validation). RESULTS FND patients were successfully distinguished from healthy controls in the replication step (accuracy of 74%) as well as in each individual additional centre (accuracies of 73%, 71% and 70%). The pooled cross validation confirmed that the classifier was robust with an accuracy of 72%. The results survived post-hoc adjustment for anxiety, depression, psychotropic medication intake, and symptom severity. The most discriminant features involved the angular- and supramarginal gyri, sensorimotor cortex, cingular- and insular cortex, and hippocampal regions. The inter-centre validation step did not exceed chance level (accuracy below 50%). CONCLUSIONS The results demonstrate the applicability of RS FC to correctly distinguish FND patients from healthy controls in different centres and its robustness against inter-scanner variability. In order to generalize its use across different centres and aim for clinical application, future studies should work towards optimization of acquisition parameters and include neurological and psychiatric control groups presenting with similar symptoms

Sex steroid hormones and epilepsy: Effects of hormonal replacement therapy on seizure frequency of postmenopausal women with epilepsy—A systematic review

Background and purpose: Hormonal replacement therapy (HRT) is used for symptomatic treatment of menopause. Some evidence suggests a proconvulsant effect of estrogen and an anticonvulsant role of progesterone. Thus, the use of exogenous sex steroid hormones might influence the course of epilepsy in peri- and postmenopausal women with epilepsy (WWE). We conducted a systematic review on the impact of HRT on the frequency of seizures of WWE. Methods: PubMed and Scopus were searched for articles published from inception until August 2022. Abstracts from the past 5 years from the European Academy of Neurology and European Epilepsy Congresses were also reviewed. Article reference lists were screened, and relevant articles were retrieved for consultation. Interventional and observational studies on WWE and animal models of estrogen deficiency were included. Critical appraisal was performed using the revised Cochrane risk-of-bias tool for randomized trials and ROBINS-E tool. Results: Of 497 articles screened, 13 studies were included, including three human studies. One cross-sectional study showed a decrease in seizure frequency in WWE using combined HRT, a case–control study showed an increase in comparison with controls, and a randomized clinical trial found a dose-dependent increase in seizure frequency in women with focal epilepsy taking combined HRT. Ten studies addressing the impact of HRT in rat models were also included, which showed conflicting results. Conclusions: There is scarce evidence of the impact of HRT in WWE. Further studies should evaluate the harmful potential, and prospective registries are needed for monitoring this population

Development of a diagnostic checklist to identify functional cognitive disorder versus other neurocognitive disorders

Background: Functional cognitive disorder (FCD) poses a diagnostic challenge due to its resemblance to other neurocognitive disorders and limited biomarker accuracy. We aimed to develop a new diagnostic checklist to identify FCD versus other neurocognitive disorders. Methods: The clinical checklist was developed through mixed methods: (1) a literature review, (2) a three-round Delphi study with 45 clinicians from 12 countries and (3) a pilot discriminative accuracy study in consecutive patients attending seven memory services across the UK. Items gathering consensus were incorporated into a pilot checklist. Item redundancy was evaluated with phi coefficients. A briefer checklist was produced by removing items with >10% missing data. Internal validity was tested using Cronbach’s alpha. Optimal cut-off scores were determined using receiver operating characteristic curve analysis. Results: A full 11-item checklist and a 7-item briefer checklist were produced. Overall, 239 patients (143 FCD, 96 non-FCD diagnoses) were included. The checklist scores were significantly different across subgroups (FCD and other neurocognitive disorders) (F(2, 236)=313.3, p0.80). Conclusions: This pilot study shows that a brief clinical checklist may serve as a quick complementary tool to differentiate patients with neurodegeneration from those with FCD. Prospective blind large-scale validation in diverse populations is warranted.Cite No

Perspectives on the diagnosis and management of functional cognitive disorder: An international Delphi study

Background: Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions. Methods: International experts in cognitive disorders were invited to assess seven illustrative clinical vignettes containing history and bedside characteristics alone. Participants assigned a probable diagnosis and selected the appropriate investigation and treatment. Qualitative, quantitative and inter‐rater agreement analyses were undertaken. Results: Eighteen diagnostic terminologies were assigned by 45 cognitive experts from 12 countries with a median of 13 years of experience, across the seven scenarios. Accurate discrimination between FCD and neurodegeneration was observed, independently of background and years of experience: 100% of the neurodegenerative vignettes were correctly classified and 75%–88% of the FCD diagnoses were attributed to non‐neurodegenerative causes. There was <50% agreement in the terminology used for FCD, in comparison with 87%–92% agreement for neurodegenerative syndromes. Blood tests and neuropsychological evaluation were the leading diagnostic modalities for FCD. Diagnostic communication, psychotherapy and psychiatry referral were the main suggested management strategies in FCD. Conclusions: Our study demonstrates the feasibility of distinguishing between FCD and neurodegeneration based on relevant patient characteristics and history details. These characteristics need further validation and operationalisation. Heterogeneous labelling and framing pose clinical and research challenges reflecting a lack of agreement in the field. Careful consideration of FCD diagnosis is advised, particularly in the presence of comorbidities. This study informs future research on diagnostic tools and evidence‐based interventions

Functional neurological disorder is a feminist issue

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