BACKGROUND: In recent years, the scientific evidence supporting a relationship between the microbiota and various diseases has increased significantly; this trend has also been observed for neurological diseases. This has given rise to the concept of the gut-brain axis and the idea of a relationship between the gut microbiota and several neurological diseases whose aetiopathogenesis is yet to be clearly defined.
METHODS: We review the role of the gut microbiota in the gut-brain axis and analyse those neurological diseases in which alterations in the gut microbiota have been described as a result of human studies: specifically, Parkinson\'s disease, Alzheimer disease, amyotrophic lateral sclerosis, neuromyelitis optica, and multiple sclerosis.
CONCLUSIONS: The body of evidence linking the gut microbiota to various neurological diseases has grown considerably. Several interesting studies show a relationship between the gut microbiota and Parkinson\'s disease, Alzheimer disease, neuromyelitis optica, and multiple sclerosis, whereas other controversial studies implicate it in amyotrophic lateral sclerosis. Many of these studies place considerable emphasis on modulation of inflammation, particularly by bacteria capable of producing short-chain fatty acids. Despite these encouraging results, many questions remain, and there is a need to demonstrate causality, determine the role of fungi or viruses, and research possible treatment through diet, probiotics, or faecal microbiota transplantation.

BACKGROUND: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson\'s disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis.
OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression.
METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales.
RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38+ in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases.
CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.

OBJECTIVE: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life.
METHODS: We conducted a retrospective observational study of patients with Parkinson\'s disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs.
RESULTS: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years±8.43 and H&Y stage was 3 [2-4]. Mean dose of levodopa used was 703.75mg±233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation.
CONCLUSIONS: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.

OBJECTIVE: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson\'s Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients.
METHODS: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals.
RESULTS: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status.
CONCLUSIONS: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.

BACKGROUND: and Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson\'s disease.
BACKGROUND: Parkinson\'s disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains.
METHODS: We retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson\'s Disease Rating Scale and the Hoehn and Yahr scale.
RESULTS: Participants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task.
CONCLUSIONS: We found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD.

Parkinson\'s disease (PD) is the second most prevalent neurodegenerative disease among adults worldwide. It is characterised by the death of dopaminergic neurons in the substantia nigra pars compacta and, in some cases, presence of intracytoplasmic inclusions of α-synuclein, called Lewy bodies, a pathognomonic sign of the disease. Clinical diagnosis of PD is based on the presence of motor alterations. The treatments currently available have no neuroprotective effect. The exact causes of PD are poorly understood. Therefore, more precise preclinical models have been developed in recent years that use induced pluripotent stem cells. In vitro studies can provide new information on PD pathogenesis and may help to identify new therapeutic targets or to develop new drugs.

BACKGROUND: LRRK2 mutations have traditionally been associated with a benign phenotype of Parkinson\'s disease (PD). Favourable responses to deep brain stimulation (DBS) are reported in the advanced phase.
METHODS: We performed a retrospective analysis of the clinical characteristics and progression of 13 patients with LRRK2-associated PD (13 with G2019S and one with I1371 V). Nine patients were in the advanced phase, with a mean progression time of 7.2 years before reaching this phase.
RESULTS: Seven patients underwent bilateral subthalamic DBS implantation, and two received infusion treatment. Patients with mutation G2019S responded excellently to DBS, with Unified Parkinson\'s disease rating scale (UPDRS) II and III scores improving by 80% at six months. This response was sustained over time. The patient with mutation I1371 V had a severe phenotype of the disease, and presented a moderate response to DBS. Patients with advanced LRRK2-associated PD showed predominantly frontal cognitive involvement, with significant language impairment.
CONCLUSIONS: In these patients, progression was faster in the advanced stage of the disease. We emphasise the suitability of subthalamic DBS in the management of these patients.

BACKGROUND: STAT-ON™ is an objective tool that registers ON-OFF fluctuations making possible to know the state of the patient at every moment of the day in normal life. Our aim was to analyze the opinion of different Parkinson\'s disease experts about the STAT-ON™ tool after using the device in a real clinical practice setting (RCPS).
METHODS: STAT-ON™ was provided by the Company Sense4Care to Spanish neurologists for using it in a RCPS. Each neurologist had the device for at least three months and could use it in PD patients at his/her own discretion. In February 2020, a survey with 30 questions was sent to all participants.
RESULTS: Two thirds of neurologists (53.8% females; mean age 44.9±9 years old) worked in a Movement Disorders Unit, the average experience in PD was 16±6.9 years, and 40.7% of them had previously used other devices. A total of 119 evaluations were performed in 114 patients (range 2-9 by neurologist; mean 4.5±2.3). STAT-ON™ was considered \"quite\" to \"very useful\" by 74% of the neurologists with an overall opinion of 6.9±1.7 (0, worst; 10, best). STAT-ON™ was considered better than diaries by 70.3% of neurologists and a useful tool for the identification of patients with advanced PD by 81.5%. Proper identification of freezing of gait episodes and falls were frequent limitations reported.
CONCLUSIONS: STAT-ON™ could be a useful device for using in PD patients in clinical practice.

BACKGROUND: Understanding alterations to brain anatomy and cognitive function associated with neurodegenerative diseases remains a challenge for neuroscience today. In experimental neuroscience, several computerised tests have been developed to contribute to our understanding of neural networks involved in cognition. The Attention Network Test (ANT) enables us to measure the activity of 3 attentional networks (alertness, orienting, and executive function).
OBJECTIVE: The main aim of this review is to describe all the anatomical and functional alterations found in diverse neurological diseases using the ANT.
METHODS: We collected studies published since 2010 in the PubMed database that employed the ANT in different neurological diseases. Thirty-two articles were obtained, addressing multiple sclerosis, epilepsy, and Parkinson\'s disease, among other disorders.
CONCLUSIONS: Some of the anatomical structures proposed in the 3 attentional networks model were confirmed. The most relevant structures in the alertness network are the prefrontal cortex, parietal region, thalamus, and cerebellum. The thalamus is also relevant in the orienting network, together with posterior parietal regions. The executive network does not depend exclusively on the prefrontal cortex and anterior cingulate cortex, but also involves such subcortical structures as the basal ganglia and cerebellum and their projections towards the entire cortex.

BACKGROUND: Unilateral Gamma Knife™ stereotactic radiosurgery on the ventral-intermediate nucleus of the thalamus is a minimally invasive neurosurgical option for refractory tremor. We describe the experience of Gamma Knife™ thalamotomy (GKT) in patients with essential tremor (ET) and tremor-dominant Parkinson\'s disease (PD) at our specialised stereotactic neurosurgery unit.
METHODS: We reviewed the cases of patients treated with GKT between January 2014 and February 2018 with a minimum of 12 months\' follow-up. We analysed clinical and demographic variables, indication, radiation dose, effectiveness (based on subscales of the Fahn-Tolosa-Marin [FTM] scale and the Movement Disorders Society-Unified Parkinson\'s Disease Rating Scale [MDS-UPDRS] motor score), and adverse events.
RESULTS: Thirteen patients were registered, 6 with a diagnosis of tremor-dominant PD, four with refractory ET, and three with ET and PD. Median age was 78 years (range, 62-83), with seven patients aged over 75 years. Four patients were receiving anticoagulants and two had history of stroke. The maximum radiation dose administered was 130 Gy. Mean (standard deviation) follow-up duration was 30.0 (14.5) months. Significant tremor improvement was observed on the FTM subscales: 63.6% at 12 months and 63.5% at the end of follow-up; MDS-UPDRS tremor items showed improvements of 71.3% at 12 months and 60.3% at the end of follow up. Eleven patients reported significant improvements in quality of life, and 3 reported mild and transient adverse effects.
CONCLUSIONS: This is the largest series of patients with essential and parkinsonian tremor treated with GKT and followed up in the long term in Spain. GKT can be safe and effective in the long term in patients with refractory tremor, including in elderly patients and those receiving anticoagulants.