Neuropsychiatric and cognitive symptoms in Parkinson’s disease: the contribution to subtype classification, to differential diagnosis, their clinical and instrumental correlations

Il piano di ricerca è volto ad approfondire il contributo dei sintomi neuropsichiatrici e cognitivi nelle diverse fasi della Malattia di Parkinson (MP). In particolare, l’argomento di studio è focalizzato sull’analisi dei sintomi cognitivi e neuropsichiatrici nella MP, affrontando queste tematiche anche mediante l’utilizzo di tecniche di neuroimaging, in pazienti drug-naïve, in fase precoce di malattia ed in fase avanzata. Nei pazienti drug-naïve, la ricerca è stata finalizzata alla caratterizzazione dei sintomi neuropsichiatrici e cognitivi nei sottotipi motori (i.e., tremorigeni vs acinetico-rigidi) e rispetto alla lateralità di esordio degli stessi (i.e., lateralità destra vs lateralità sinistra). Nei pazienti in fase precoce di malattia, è stato indagato il contributo dei sintomi neuropsichiatrici e cognitivi nella diagnosi differenziale tra MP e Paralisi Sopranucleare Progressiva (PSP) in pazienti valutati entro i 24 mesi dall’esordio motorio, finestra temporale in cui spesso si assiste ad un overlapping dei sintomi motori. Nei pazienti in fase avanzata di malattia, la ricerca è stata finalizzata alla caratterizzazione, mediante i sintomi neuropsichiatrici e cognitivi, del Gioco D’Azzardo Patologico (gambling) rispetto agli altri tipi di Disturbi del controllo degli Impulsi (ICDs). Ancora nell’ambito dell’ICDs, è stato sviluppato uno studio di neuroimaging, volto ad identificare i correlati morfostrutturali (spessori corticali e volumi dei nuclei sottocorticali) di tali disturbi. Infine, si sono identificati i sintomi neuropsichiatrici e cognitivi che possono impedire l’esecuzione di un esame di Risonanza Magnetica (RM), al fine, in ambito clinico, di preparare adeguatamente all’esame i pazienti più a rischio di mancato svolgimento e con l’intento di indagare, in ambito di ricerca, la reale rappresentatività campionaria dei pazienti inseriti in studi di RM

The Dopaminergic System in Peripheral Blood Lymphocytes: From Physiology to Pharmacology and Potential Applications to Neuropsychiatric Disorders

Besides its action on the nervous system, dopamine (DA) plays a role on neural-immune interactions. Here we review the current evidence on the dopaminergic system in human peripheral blood lymphocytes (PBL). PBL synthesize DA through the tyrosine-hydroxylase/DOPA-decarboxylase pathway, and express DA receptors and DA transporter (DAT) on their plasma membrane. Stimulation of DA receptors on PBL membrane contributes to modulate the development and initiation of immune responses under physiological conditions and in immune system pathologies such as autoimmunity or immunodeficiency. The characterization of DA system in PBL gave rise to a further line of research investigating the feasibility of PBL as a cellular model for studying DA derangement in neuropsychiatric disorders. Several reports showed changes of the expression of DAT and/or DA receptors in PBL from patients suffering from several neuropsychiatric disorders, in particular parkinsonian syndromes, schizophrenia and drug-or alcohol-abuse. Despite some methodological and theoretical limitations, these findings suggest that PBL may prove a cellular tool with which to identify the derangement of DA transmission in neuropsychiatric diseases, as well as to monitor the effects of pharmacological treatments

Prodromal non-motor symptoms of Parkinson’s disease

The motor symptoms of Parkinson’s disease (PD), bradykinesia, muscular rigidity, and tremor depend upon degeneration of the dopaminergic neurons in the substantia nigra pars compacta. Recent neuropathological studies show that the Lewy bodies, the intraneuronal landmark of PD, accumulate in several neuronal cell types in the brain. An ascending gradient of pathological involvement, from the medulla oblongata to neocortical areas has been reported. Thus the original view of PD as a disease characterized by selective damage of the dopaminergic neurons in the mesencephalon should be updated into the concept of a severe multisystemic neurodegenerative disorder. Additionally, the neuropathological alterations outside the substantia nigra are soundly correlated with the non-motor symptoms of PD. As a result of these findings, interest is growing in the identification of prodromal non-motor symptoms of PD. Indeed, data from the literature suggest that autonomic disturbances, olfactory dysfunctions, depression and sleep disorders (in particular REM-sleep behavior disorder) may represent prodromal non-motor symptoms of PD. Several tests are available to detect most of these symptoms. Thus, the identification of prodromal non-motor symptoms may contribute to the precocious diagnosis of PD, and might be useful in the future to test the efficacy of neuroprotective agents

Foot Pressure Wearable Sensors for Freezing of Gait Detection in Parkinson’s Disease

Freezing of Gait (FoG) is a common symptom in Parkinson's Disease (PD) occurring with significant variability and severity and is associated with increased risk of falls. FoG detection in everyday life is not trivial, particularly in patients manifesting the symptom only in specific conditions. Various wearable devices have been proposed to detect PD symptoms, primarily based on inertial sensors. We here report the results of the validation of a novel system based on a pair of pressure insoles equipped with a 3D accelerometer to detect FoG episodes. Twenty PD patients attended a motor assessment protocol organized into eight multiple video recorded sessions, both in clinical and ecological settings and both in the ON and OFF state. We compared the FoG episodes detected using the processed data gathered from the insoles with those tagged by a clinician on video recordings. The algorithm correctly detected 90% of the episodes. The false positive rate was 6% and the false negative rate 4%. The algorithm reliably detects freezing of gait in clinical settings while performing ecological tasks. This result is promising for freezing of gait detection in everyday life via wearable instrumented insoles that can be integrated into a more complex system for comprehensive motor symptom monitoring in PD

Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study.

peer reviewed[en] BACKGROUND: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated. OBJECTIVE: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group. METHODS: Cerebellar parcellation was performed using a deep learning-based approach from 2487 people with PD and 1212 age and sex-matched controls across 22 sites. Linear mixed effects models compared total and regional cerebellar volume in people with PD at each Hoehn and Yahr (HY) disease stage, to an age- and sex- matched control group. Associations with motor symptom severity and Montreal Cognitive Assessment scores were investigated. RESULTS: Overall, people with PD had a regionally smaller posterior lobe (dmax  = -0.15). HY stage-specific analyses revealed a larger anterior lobule V bilaterally (dmax  = 0.28) in people with PD in HY stage 1 compared to controls. In contrast, smaller bilateral lobule VII volume in the posterior lobe was observed in HY stages 3, 4, and 5 (dmax  = -0.76), which was incrementally lower with higher disease stage. Within PD, cognitively impaired individuals had lower total cerebellar volume compared to cognitively normal individuals (d = -0.17). CONCLUSIONS: We provide evidence of a dissociation between anterior "motor" lobe and posterior "non-motor" lobe cerebellar regions in PD. Whereas less severe stages of the disease are associated with larger motor lobe regions, more severe stages of the disease are marked by smaller non-motor regions

Novelle calabresi

Novelle calabresi / Clelia Pellicano (Jane Grey). - Torino : Societa tipografico-editrice Nazionale, 1908 Dedica manoscritta dell'autore: Ad Emilio Bodrero, / amichevole omaggio / di Jane Grey https://galileodiscovery.unipd.it/discovery/fulldisplay?context=L&vid=39UPD_INST:VU1&search_scope=MyInst_and_CI&tab=Everything&docid=alma99001179786020604

Neuropharmacology and behavior in planaria: translations to mammals

Planarians are the simplest animals to exhibit a body plan common to all vertebrates and many invertebrates, characterized by bilateral rather than radial symmetry, dorsal and ventral surfaces, and a rostrocaudal axis with a head and a tail, including specialized sense organs and an aggregate of nerve cells in the head. Neurons in planarian more closely resemble those of vertebrates than those of advanced invertebrates, exhibiting typical vertebrate features of multipolar shape, dendritic spines with synaptic boutons, a single axon, expression of vertebrate-like neural proteins, and relatively low spontaneously generated electrical activity. Here we report the most relevant contribution to the knowledge of the neuropharmacology of planarians, with particular reference to the behavioral consequences of the exposure to drugs acting on neural transmission. Neurochemical and histochemical data indicate the presence of several neurotransmitter-receptor systems in planarians. Moreover, a variety of experimental studies characterized specific behavioral patterns of these animals following the exposure to drugs acting on neural transmission. There is also evidence of the interactions between discrete neurotransmitter-receptor systems in modulating behavior in planarians. Finally, the model has proved efficacy for investigating the neurotoxicology of the dopamine neurons, and for the initial screening of the neuroprotective potential of drugs. In conclusion, these findings indicate that interactions between discrete neurotransmitter-receptor systems occur very early along phylogeny, although they may have evolved from very fundamental behaviors, such as motor activity in planarian, to more complex and integrated functions in vertebrates

Bupropion abates dopamine agonist-mediated compulsive behaviors in Parkinson's disease.

Compulsive behaviors are relatively frequent complications of Parkinson’s disease (PD).1 Risk factors for compulsive behaviors in PD include novelty-seeking personality traits, depressive symptoms, young age, and cumulative dose of dopaminergic drugs, in particular dopamine agonists (DA). Although the pathophysiology of DA-mediated compulsive behaviors in PD is not completely defined at present, altered and pulsatile mesolimbic dopaminergic stimulation may play a fundamental rol

Tako tsubo and ischemic stroke in a patient with Alzheimer’s disease

Background Tako-tsubo cardiomyopathy (TTC), also known as "stress induced cardiomyopathy", is an acute cardiac condition characterized by transient myocardial dysfunction associated with a peculiar pattern of reversibile left ventricular ballooning that mimics myocardial infarction, but with normal coronary arteries. Tako-tsubo cardiomyopathy typically occurs in postmenopausal women and it is often triggered by physical or emotional stressful events. We report on a patient with Alzheimer's disease, who presented with TTC and an ischemic stroke. © 2014 Springer International Publishing Switzerland