Sintomi non motori e disautonomia cardiovascolare in pazienti sardi affetti da malattia di parkinson con e senza mutazioni del gene LRRK2

Background: Although Parkinson’s disease (PD) is commonly described as a motor disorder, non-motor symptoms and cardiovascular dysautonomia are important factors of disability and impaired quality of life in PD patients. To date, the definite correlation of cardiovascular symptoms with motor and other non-motor symptoms of PD are still largely unclear. Besides, the discovery of genetic mutations related to PD, such as LRRK2 mutations, provides better possibility to identify specific phenotypes both for motor and non-motor symptoms. Obiectives: The main objective of our study was directed to investigate the presence and the correlation of cardiovascular dysautonomia with other non-motor symptoms in PD patients, with with or without LRRK2 mutations. Finally, we performed a study of heart rate variability (HRV) and exercise stress echocardiography with the attempt to investigate dysautonomia in these groups of patients. Methods: Forty fifteen Sardinian PD patients (240 men and 165 women) were included in the study. PD patients were screened for the presence of LRRK2 mutations. Motor impairment and disability were assessed using the Hoehn & Yahr staging and the Unified PD Rating Scale (UPDRS) part-III. Cardiovascular symptoms and other non-motor symptoms were assessed with the Non-Motor Symptoms Scale (NMSS). Correlations between cardiovascular symptoms and other PD features were studied. Heart rate variability (HRV) and exercise stress echocardiography were performed in two subgroups of patients (with or without LRRK2 mutations) and in a control group, matched for age and gender. Results: Cardiovascular symptoms were among the five non-motor symptoms more reported and were correlated with multiple non motor symptoms, especially with fatigue and loss of weight. PD patients with LRRK2 mutations reported less severity of cardiovascular symptoms. HRV revealed reduced LF/HF ratio both in PD patients with or without LRKK2 mutations, with enhancement of HF in LRRK2 patients. Cardiovascular symptoms detected at NMSS correlated with LF/HF ratio. Echocardiography show a Δ Strain rate reduced in parkinsonian patients. Δ Strain rate was also correlated with the LF/HF ratio in the LRRK2 group. Discussion: The better assessment of non-motor and cardiovascular symptoms in PD patients with and without LRRK2 mutation, both with the systematic administration of symptomatic scales, such as the NMSS, and with a combined approach with HRV and exercise stress echocardiography, might lead to the detection of better monitoring systems and to the possible improvement of current strategies used in the treatment of these disabling conditions

Sintomi non motori e disautonomia cardiovascolare in pazienti sardi affetti da malattia di parkinson con e senza mutazioni del gene LRRK2

Background: Although Parkinson’s disease (PD) is commonly described as a motor disorder, non-motor symptoms and cardiovascular dysautonomia are important factors of disability and impaired quality of life in PD patients. To date, the definite correlation of cardiovascular symptoms with motor and other non-motor symptoms of PD are still largely unclear. Besides, the discovery of genetic mutations related to PD, such as LRRK2 mutations, provides better possibility to identify specific phenotypes both for motor and non-motor symptoms. Obiectives: The main objective of our study was directed to investigate the presence and the correlation of cardiovascular dysautonomia with other non-motor symptoms in PD patients, with with or without LRRK2 mutations. Finally, we performed a study of heart rate variability (HRV) and exercise stress echocardiography with the attempt to investigate dysautonomia in these groups of patients. Methods: Forty fifteen Sardinian PD patients (240 men and 165 women) were included in the study. PD patients were screened for the presence of LRRK2 mutations. Motor impairment and disability were assessed using the Hoehn & Yahr staging and the Unified PD Rating Scale (UPDRS) part-III. Cardiovascular symptoms and other non-motor symptoms were assessed with the Non-Motor Symptoms Scale (NMSS). Correlations between cardiovascular symptoms and other PD features were studied. Heart rate variability (HRV) and exercise stress echocardiography were performed in two subgroups of patients (with or without LRRK2 mutations) and in a control group, matched for age and gender. Results: Cardiovascular symptoms were among the five non-motor symptoms more reported and were correlated with multiple non motor symptoms, especially with fatigue and loss of weight. PD patients with LRRK2 mutations reported less severity of cardiovascular symptoms. HRV revealed reduced LF/HF ratio both in PD patients with or without LRKK2 mutations, with enhancement of HF in LRRK2 patients. Cardiovascular symptoms detected at NMSS correlated with LF/HF ratio. Echocardiography show a Δ Strain rate reduced in parkinsonian patients. Δ Strain rate was also correlated with the LF/HF ratio in the LRRK2 group. Discussion: The better assessment of non-motor and cardiovascular symptoms in PD patients with and without LRRK2 mutation, both with the systematic administration of symptomatic scales, such as the NMSS, and with a combined approach with HRV and exercise stress echocardiography, might lead to the detection of better monitoring systems and to the possible improvement of current strategies used in the treatment of these disabling conditions

Therapeutic interventions and adjustments in the management of Parkinson disease: role of combined carbidopa/levodopa/entacapone (Stalevo®)

Parkinson disease (PD) is a neurodegenerative disorder characterized by 3 cardinal motor symptoms: resting tremor, rigidity, and bradykinesia. Since its introduction 40 years ago, levodopa has represented the gold standard for dopaminergic stimulation therapy in patients with PD. Levodopa is routinely combined with a dopa-decarboxylase inhibitor (DDCI) to prevent the conversion of levodopa into dopamine in peripheral circulation. However, up to 80% of patients treated with continuous levodopa manifest the onset of disabling motor complications capable of producing an adverse effect on quality of life as the disease progresses. In recent years, a new, safe, and efficacious armamentarium of treatment options has been provided by the marketing of the catechol-O-methyltransferase (COMT) inhibitor, entacapone, a peripheral blocker of dopa to 3-0-methyldopa metabolism, which increments levodopa brain availability. When administered with levodopa, entacapone conjugates the rapid onset of levodopa-induced effects with a protracted efficiency, thus providing additional benefits to classic levodopa treatment by increasing “on” time in fluctuating PD patients, and theoretically providing a more continuous and physiological-like stimulation of dopamine receptors implying a reduced risk of motor complications. In this context, the use of a single administration of combined carbidopa/ levodopa/entacapone (Stalevo®) in the treatment of PD affords clinical improvements similar to those obtained by 2 separate tablets (ie, levodopa/DDCI and entacapone), although the former produces a more positive effect on quality of life than the latter. Additionally, the STalevo Reduction In Dyskinesia Evaluation (STRIDE-PD) study was designed with the aim of demonstrating that the combination of levodopa, carbidopa, and entacapone, used as initial levodopa therapy, significantly delays the onset of dyskinesias compared with the conventional levodopa/carbidopa formulation. Unfortunately, STRIDEPD failed to prove the benefit of continuous dopaminergic stimulation with triple therapy in a clinical setting. Recently, the effect of combined COMT inhibitor with levodopa administration in reducing homocysteine synthesis has been described. To this regard, clear evidence has been presented indicating homocysteine as a risk factor for vascular diseases, cognitive impairment, and dementia. Several studies have discussed the potential of entacapone as adjunct to levodopa/ DDCI in reducing plasma homocysteine levels with contrasting results

Structure and morphology of shape-controlled Pd nanocrystals

Pd nanocrystals were produced with uniform truncated-cube shape and a narrow size distribution, yielding controlled surface area fractions from low Miller index ({100}, {110}, {111}) crystalline facets. Details on the structure and morphology of the nanocrystals were obtained by combining X-ray powder diffraction line profile analysis, high-resolution transmission electron microscopy and surface electrochemistry based on Cu underpotential deposition.ML acknowledges support from the Italian government (Ministero dell’Istruzione, dell’Università e della Ricerca) through the project FIRB Futuro in Ricerca RBFR10CWDA. JMF acknowledges financial support from the MINECO (Spain) project CTQ2013-44083-P and Generalitat Valenciana project PROMETEOII/2014/013

Qualitative smell/taste disorders as sequelae of acute COVID-19

Background Qualitative smell/taste disorders (such as phantosmia, parosmia, phantogeusia, and parageusia) have not yet been fully characterized in patients who had COVID-19, whereas quantitative disturbances (i.e., reduction/loss of smell/taste) have been widely investigated. Objective To simultaneously assess the presence of both quantitative and qualitative smell/taste dysfunctions in patients who suffered from COVID-19. Methods We enrolled 17 consecutive patients who suffered from COVID-19 over the last 6 months and 21 healthy controls, matched for sex and age. After a negative nasopharyngeal swab, the Sniffin’ Sticks Test and the Taste Strips were used to assess olfactory and taste function, respectively. At the same time, the presence of phantosmia, parosmia, phantogeusia, and parageusia was investigated with a standardized questionnaire. Results Qualitative disturbances of smell and/or taste were found in 6/17 (35.3%) patients. Phantosmia was reported in 2/17 (11.8%) patients and parosmia in 4/17 (23.5%). There were no significant differences in smell test scores between patients who reported phantosmia and/or parosmia and patients who did not. Phantogeusia was described in 3/17 (17.6%) patients, and parageusia was identified in 4/17 (23.5%) patients. All tested patients were normogeusic. Conclusion Around one-third of patients who recover from COVID-19 may have persistent qualitative dysfunction in smell/taste domains. Detection of phantogeusia in long-term COVID-19 patients represents a further novel finding. Further investigation is needed to better characterize the pathophysiology of phantosmia, parosmia, phantogeusia, and parageusia in patients who had COVID-19

Drosophila mutant model of Parkinson's disease revealed an unexpected olfactory performance: Morphofunctional evidences

Parkinson's disease (PD) is one of the most common neurodegenerative diseases characterized by the clinical triad: tremor, akinesia, and rigidity. Several studies have suggested that PD patients show disturbances in olfaction as one of the earliest, nonspecific nonmotor symptoms of disease onset. We sought to use the fruit fly Drosophila melanogaster as a model organism to explore olfactory function in LRRK loss-of-function mutants, which was previously demonstrated to be a useful model for PD. Surprisingly, our results showed that the LRRK mutant, compared to the wild flies, presents a dramatic increase in the amplitude of the electroantennogram responses and this is coupled with a higher number of olfactory sensilla. In spite of the above reported results, the behavioural response to olfactory stimuli in mutant flies is impaired compared to that obtained in wild type flies. Thus, behaviour modifications and morphofunctional changes in the olfaction of LRRK loss-of-function mutants might be used as an index to explore the progression of parkinsonism in this specific model, also with the aim of studying and developing new treatment

An unusual delusion of duplication in a patient affected by Dementia with Lewy bodies

Background: Dementia with Lewy bodies (DLB) is the second most frequent diagnosis of progressive degenerative dementia in older people. Delusions are common features in DLB and, among them, Capgras syndrome represents the most frequent disturbance, characterized by the recurrent and transient belief that a familiar person, often a close family member or caregiver, has been replaced by an identical-looking imposter. However, other delusional conditions near to misidentification syndromes can occur in DLB patients and may represent a major psychiatric disorder, although rarely studied systematically. Case presentation: We reported on a female patient affected by DLB who presented with an unusual delusion of duplication. Referring to the female professional caregiver engaged by her relatives for her care, the patient constantly described the presence of two different female persons, with a disorder framed in the context of a delusion of duplication. A brain 99Tc-hexamethylpropyleneamineoxime SPECT was performed showing moderate hypoperfusion in both occipital lobes, and associated with marked decreased perfusion in parieto-fronto-temporal lobes bilaterally. Conclusions: An occipital hypoperfusion was identified, although in association with a marked global decrease of perfusion in the remaining lobes. The role of posterior lobes is certainly important in all misidentification syndromes where a natural dissociation between recognition and identification is present. Moreover, the concomitant presence of severe attentional and executive deficits evocative for a frontal syndrome and the marked global decrease of perfusion in the remaining lobes at the SPECT scan also suggest a possible dysfunction in an abnormal connectivity between anterior and posterior areas

Frequency and Determinants of Olfactory Hallucinations in Parkinson’s Disease Patients

Background: Olfactory dysfunctions and hallucinations are considered common nonmotor symptoms in Parkinson’s disease (PD). Visual and auditory hallucinations are well-known; however, olfactory hallucinations (OHs) are not fully investigated. The aim of this study was to evaluate OHs in PD patients, and their correlation to motor impairment, cognitive abilities, visual and auditory hallucinations, and olfactory and gustatory function. Methods: A sample of 273 patients was enrolled: 141 PD patients (mean age SD: 70.1 9.5 years) and 132 healthy controls (mean age SD: 69.4 9.6 years). In all patients, the following parameters were evaluated: motor symptoms (UPDRSIII), olfactory function, cognitive abilities, and occurrence of OH, gustatory hallucinations (GHs), and visual/auditory hallucinations. Results: OHs were found only in PD patients with a percentage of 11.3%. Among PD patients with OHs, 2.8% also presented GHs. High significant frequencies of females, the presence of visual/auditory hallucinations, and a high mean UPDRS-III score were found in patients with OHs related to patients without them. Binary logistic regression evidenced the presence of visual/auditory hallucinations and sex as main variables predicting the presence of OHs. Conclusions: Our data indicated that OHs occur frequently in PD patients, especially in women, and often concomitant with visual and auditory hallucinations, without any association with olfactory impairment

Serum and cerebrospinal fluid biomarkers in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein associated disease

The term neuromyelitis optica spectrum disorder (NMOSD) describes a group of clinical-MRI syndromes characterized by longitudinally extensive transverse myelitis, optic neuritis, brainstem dysfunction and/or, less commonly, encephalopathy. About 80% of patients harbor antibodies directed against the water channel aquaporin-4 (AQP4-IgG), expressed on astrocytes, which was found to be both a biomarker and a pathogenic cause of NMOSD. More recently, antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG), have been found to be a biomarker of a different entity, termed MOG antibody-associated disease (MOGAD), which has overlapping, but different pathogenesis, clinical features, treatment response, and prognosis when compared to AQP4-IgG-positive NMOSD. Despite important refinements in the accuracy of AQP4-IgG and MOG-IgG testing assays, a small proportion of patients with NMOSD still remain negative for both antibodies and are called "seronegative" NMOSD. Whilst major advances have been made in the diagnosis and treatment of these conditions, biomarkers that could help predict the risk of relapses, disease activity, and prognosis are still lacking. In this context, a number of serum and/or cerebrospinal fluid biomarkers are emerging as potentially useful in clinical practice for diagnostic and treatment purposes. These include antibody titers, cytokine profiles, complement factors, and markers of neuronal (e.g., neurofilament light chain) or astroglial (e.g., glial fibrillary acidic protein) damage. The aim of this review is to summarize current evidence regarding the role of emerging diagnostic and prognostic biomarkers in patients with NMOSD and MOGAD

Citrate-coated, size-tunable octahedral platinum nanocrystals: a novel route for advanced electrocatalysts

The development of green and scalable syntheses for the preparation of size- and shape-controlled metal nanocrystals is of high interest in many areas, including catalysis, electrocatalysis, nanomedicine, and electronics. In this work, a new synthetic approach based on the synergistic action of physical parameters and reagents produces size-tunable octahedral Pt nanocrystals, without the use of catalyst-poisoning reagents and/or difficult-to-remove coatings. The synthesis requires only sodium citrate, ascorbic acid, and fine control of the reduction rate in aqueous environment. Pt octahedral nanocrystals with particle size as low as 7 nm and highly developed {111} facets have been achieved, as demonstrated by Transmission Electron Microscopy, X-ray Diffraction, and electrochemical methods. The absence of sticky molecules together with the high quality of the surface renders these nanocrystals ideal candidates in electrocatalysis. Notably, 7 nm bismuth-decorated octahedral nanocrystals exhibit superior performance for the electro-oxidation of formic acid in terms of both specific and mass activities.JMF and VM acknowledge financial support from MINECO (projects CTQ2016-76221-P and CTQ2016-76231-C2-2-R (AEI/FEDER, UE)). JSG acknowledges financial support from VITC (Vicerrectorado de Investigación y Transferencia de Conocimiento) of the University of Alicante (UATALENTO16-02)