The gut-brain axis is increasingly recognized as an important pathway of communication and of physiological regulation, and gut microbiota seems to play a significant role in this mutual relationship. Oxidative stress is one of the most important pathogenic mechanisms for both neurodegenerative diseases, such as Alzheimer's or Parkinson's, and acute conditions, such as stroke or traumatic brain injury. A peculiar microbiota type might increase brain inflammation and reactive oxygen species levels and might favor abnormal aggregation of proteins. Reversely, brain lesions of various etiologies result in alteration of gut properties and microbiota. These recent hypotheses could open a door for new therapeutic approaches in various neurological diseases.

Parkinson’s disease (PD) is characterized by alpha-synuclein misfolding with subsequent intraneuronal amyloid formation and accumulation, low grade neuroinflammatory changes, and selective neurodegeneration. Available evidence suggests that the pathology usually begins in the gut and olfactory mucosa, spreading to the brain via the vagus and olfactory nerves, by a prion-like mechanism. A causal relationship has not been established, but gut dysbiosis is prevalent in PD and may lead to intestinal inflammation and barrier dysfunction. Additionally, epidemiological data indicate a link between inflammatory bowel diseases and PD. Calprotectin and zonulin are markers of intestinal inflammation and barrier permeability, respectively. We evaluated their serum and fecal levels in 22 patients with sporadic PD and 16 unmatched healthy controls. Mean calprotectin was higher in PD, both in serum (14.26 mcg/ml ± 4.50 vs. 5.94 mcg/ml ± 3.80, p = 0.0125) and stool (164.54 mcg/g ± 54.19 vs. 56.19 mcg/g ± 35.88, p = 0.0048). Mean zonulin was also higher in PD serum (26.69 ng/ml ± 3.55 vs. 19.43 ng/ml ± 2.56, p = 0.0046) and stool (100.19 ng/ml ± 28.25 vs. 37.3 ng/ml ± 13.26, p = 0.0012). Calprotectin was above the upper reference limit in 19 PD serums and 6 controls (OR = 10.56, 95% CI = 2.17–51.42, p = 0.0025) and in 20 PD stool samples and 4 controls (OR = 30, 95% CI = 4.75–189.30, p = 0.000045). Increased zonulin was found only in the stool samples of 8 PD patients. Despite the small sample size, our findings are robust, complementing and supporting other recently published results. The relation between serum and fecal calprotectin and zonulin levels and sporadic PD warrants further investigation in larger cohorts.

Increasing evidence suggests that the gut microbiota and the brain are closely connected via the so-called gut–brain axis. Small intestinal bacterial overgrowth (SIBO) is a gut dysbiosis in which the small intestine is abundantly colonized by bacteria that are typically found in the colon. Though not a disease, it may result in intestinal symptoms caused by the accumulation of microbial gases in the intestine. Intestinal inflammation, malabsorption and vitamin imbalances may also develop. SIBO can be eradicated by one or several courses of antibiotics but reappears if the predisposing condition persists. Parkinson’s disease (PD) is a common neurodegenerative proteinopathy for which disease modifying interventions are not available. Sporadic forms may start in the gut years before the development of clinical features. Increased gastrointestinal transit time is present in most people with PD early during the course of the disease, predisposing to gut dysbiosis, including SIBO. The role that gut dysbiosis may play in the etiopathogenesis of PD is not fully understood yet. Here, we discuss the possibility that SIBO could contribute to the progression of PD, by promoting or preventing neurodegeneration, thus being a potential target for treatments aiming at slowing down the progression of PD. The direct symptomatic impact of SIBO and its impact on symptomatic medication are also briefly discussed.

Background and Aim: Remote ischemic conditioning is a procedure purported to reduce the ischemic injury of an organ. This study aimed to explore the efficiency and safety of remote ischemic conditioning in patients with acute ischemic stroke. We hypothesized that remote ischemic conditioning administered from the first day of hospital admission would improve the infarct volume and clinical outcome at 180 days.Material and Methods: We performed a unicentric double-blind randomized controlled trial. We included all patients consecutively admitted to an Emergency Neurology Department with acute ischemic stroke, ineligible for reperfusion treatment, up to 24 hours from onset. All subjects were assigned to receive secondary stroke prevention treatment along with remote ischemic conditioning on the non-paretic upper limb during the first 5 days of hospitalization, twice daily - a blood pressure cuff placed around the arm was inflated to 20 mmHg above the systolic blood pressure (up to 180 mmHg) in the experimental group and 30 mmHg in the sham group. The primary outcome was the difference in infarct volume (measured on brain CT scan) at 180 days compared to baseline, whereas the secondary outcomes included differences in clinical scores (NIHSS, mRS, IADL, ADL) and cognitive/mood changes (MoCA, PHQ-9) at 180 days compared to baseline.Results: We enrolled 40 patients; the mean age was 65 years and 60% were men. Subjects in the interventional group had slightly better recovery in terms of disability, as demonstrated by the differences in disability scores between admission and 6 months (e.g., the median difference score for Barthel was −10 in the sham group and −17.5 in the interventional group, for ADL −2 in the sham group and −2.5 in the interventional group), as well as cognitive performance (the median difference score for MoCA was −2 in the sham group and −3 in the interventional group), but none of these differences reached statistical significance. The severity of symptoms (median difference score for NIHSS = 5 for both groups) and depression rate (median difference score for PHQ-9 = 0 for both groups) were similar in the two groups. The median difference between baseline infarct volume and final infarct volume at 6 months was slightly larger in the sham group compared to the interventional group (p = 0.4), probably due to an initial larger infarct volume in the former.Conclusion: Our results suggest that remote ischemic conditioning might improve disability and cognition. The difference between baseline infarct volume and final infarct volume at 180 days was slightly larger in the sham group.

Alzheimer's disease is the most common neurodegenerative disorder, and its prevalence increases with age. Although there is a large amount of scientific literature focusing on Alzheimer's disease cardinal cognitive features, autonomic nervous system dysfunction remains understudied despite being common in the elderly. In this article, we reviewed the evidence for autonomic nervous system involvement in Alzheimer's disease. We identified four major potential causes for dysautonomia in Alzheimer's disease, out of which two are well-studied (comorbidities and medication) and two are rather hypothetical (Alzheimer's pathology and brain co-pathology). Although there appears to be some evidence linking Alzheimer's disease pathology to autonomic nervous system dysfunction, there is an important gap between two types of studies; histopathologic studies do not address dysautonomia manifestations, whereas clinical studies do not employ histopathologic diagnostic confirmation. Moreover, brain co-pathology is emerging as an important confounding factor. Therefore, we consider the correlation between dysautonomia and Alzheimer's disease to be an open question that needs further study. Nevertheless, given its impact on morbidity and mortality, we emphasize the importance of assessing autonomic dysfunction in patients with Alzheimer clinical syndrome.

Introduction: The emerging Coronavirus Disease (COVID-19) pandemic caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious public health issue due to its rapid spreading, high mortality rate and lack of specific treatment. Given its unpredictable clinical course, risk assessment, and stratification for severity of COVID-19 are required. Apart from serving as admission criteria, prognostic factors might guide future therapeutic strategies.Aim: We aimed to compare clinical features and biological parameters between elderly (age ≥ 65 years) and non-elderly (age <65 years) patients with COVID-19 and new neurological symptoms/conditions. We also aimed to determine factors independently associated with all-cause in-hospital mortality.Methods: All consecutive patients with COVID-19 and new neurological symptoms/conditions admitted in our Neurology Department between April 1 and August 23, 2020 were enrolled in this observational retrospective cohort study. Patient characteristics such as demographic data, comorbidities, biological parameters, imaging findings and clinical course were recorded. All-cause in-hospital mortality was the main outcome, whereas COVID-19 severity, hospitalization duration and the levels of supplemental oxygen were the secondary outcomes.Results: One hundred forty-eight patients were included, out of which 54.1% were women. The average age was 59.84 ± 19.06 years and 47.3% were elderly, the majority having cardiovascular and metabolic comorbidities. In the elderly group, the most frequent neurological symptoms/manifestations responsible for hospitalization were stroke symptoms followed by confusion, whereas in the non-elderly, headache prevailed. The final neurological diagnosis significantly varied between the two groups, with acute cerebrovascular events and acute confusional state in dementia most commonly encountered in the elderly (65.71 and 14.28%, respectively) and secondary headache attributed to SARS-CoV-2 infection often experienced by the non-elderly (38.46%). The elderly had statistically significant higher median values of white blood cell (8,060 vs. 6,090/μL) and neutrophil count (6,060 vs. 4,125/μL), C-reactive protein (29.2 vs. 5.72 mg/L), ferritin (482 vs. 187 mg/dL), fibrinogen (477 vs. 374 mg/dL), D-dimer (1.16 vs. 0.42), prothrombin time (151.15 vs. 13.8/s), aspartate transaminase (26.8 vs. 20.8 U/l), creatinine (0.96 vs. 0.77 mg/dL), and blood urea nitrogen level (51.1 vs. 27.65 mg/dL), as well as lower median value of hemoglobin (13.05 vs. 13.9 g/dL) and lymphocyte count (1,245 vs. 1,670/μL). Moreover, advanced age was significantly associated with more extensive lung involvement (25 vs. 10%) and higher fatality rate (40 vs. 9%). Overall, the mortality rate was 23.6%. Age as well as neutrophil count, C-reactive protein, fibrinogen, and activated partial thromboplastin time levels were independently associated with mortality.Conclusions: Older age, higher neutrophil count, C-reactive protein, fibrinogen, and activated partial thromboplastin time levels are independent predictors of mortality in COVID-19 patients with new neurological manifestations/conditions at admission.

Background and objectives: Multiple sclerosis (MS) patients tend to present peculiar personality traits that highly impact their quality of life. Our study aimed to determine which personality traits are more common in MS patients compared to a sex- and age-matched control group. Methods and materials: Patients with relapsing–remitting MS along with a sex- and age-matched control group were included. All subjects completed the DECAS Personality Inventory and an additional form including demographic characteristics. Data (including descriptive statistics and univariate and multivariate analysis) were analyzed using SPSS. Results: 122 subjects were included, out of which 61 were in the patient group, mostly females (71.31%) with a mean age of 42.06 ± 10.46 years. Mean duration of disease was 10.18 ± 5.53 years and mean EDSS score was 2.09; 36% of patients were treated with Interferon-beta 1a. Subjects in the patient group presented significantly lower scores for extraversion (p = 0.036), specifically those with higher EDSS score, even after adjusting for possible confounders (age, sex, marital status, early retirement, alcohol, and tobacco consumption). Additionally, regarding orientation in life, MS patients were more often philosophers (p = 0.001), especially young males, whereas the dominant emotional feeling was less common, the actor profile (p = 0.022). Regarding task involvement, MS patients were often passive and compassionate concerning other people. Higher EDSS score also correlated with avoidant (p = 0.006) and melancholic (p = 0.043) personality traits. Subjects with higher education associated more often pragmatic, experimenter, popular, and optimist traits, whereas the elderly had actor, authoritarian, and experimenter profiles. Conclusions: Some MS patients may have reduced levels of extraversion and specific personality traits compared to age- and sex-matched subjects. Determining the exact personality profile might help the neurologist to establish a better therapeutic alliance and to apply specific interventions.

(1) Background: Cardiovascular autonomic dysfunction is a non-motor feature in Parkinson’s disease with negative impact on functionality and life expectancy, prompting early detection and proper management. We aimed to describe the blood pressure patterns reported in patients with Parkinson’s disease, as measured by 24-h ambulatory blood pressure monitoring. (2) Methods: We conducted a systematic search on the PubMed database. Studies enrolling patients with Parkinson’s disease undergoing 24-h ambulatory blood pressure monitoring were included. Data regarding study population, Parkinson’s disease course, vasoactive drugs, blood pressure profiles, and measurements were recorded. (3) Results: The search identified 172 studies. Forty studies eventually fulfilled the inclusion criteria, with 3090 patients enrolled. Abnormal blood pressure profiles were commonly encountered: high blood pressure in 38.13% of patients (938/2460), orthostatic hypotension in 38.68% (941/2433), supine hypertension in 27.76% (445/1603) and nocturnal hypertension in 38.91% (737/1894). Dipping status was also altered often, 40.46% of patients (477/1179) being reverse dippers and 35.67% (310/869) reduced dippers. All these patterns were correlated with negative clinical and imaging outcomes. (4) Conclusion: Patients with Parkinson’s disease have significantly altered blood pressure patterns that carry a negative prognosis. Ambulatory blood pressure monitoring should be validated as a biomarker of PD-associated cardiovascular dysautonomia and a tool for assisting therapeutic interventions.