Papers by Giuseppe Sancesario
Journal of Alzheimer's disease reports, Jul 27, 2023
Background: Sleep impairment has been commonly reported in Alzheimer's disease (AD) patients. The... more Background: Sleep impairment has been commonly reported in Alzheimer's disease (AD) patients. The association between sleep dysregulation and AD biomarkers has been separately explored in mild cognitive impairment (MCI) and AD patients. Objective: The present study investigated cerebrospinal-fluid (CSF) and 18 F-fluoro-deoxy-glucose positron emission tomography (18 F-FDG-PET) biomarkers in MCI and AD patients in order to explore their association with sleep parameters measured with polysomnography (PSG). Methods: MCI and AD patients underwent PSG, 18 F-FDG-PET, and CSF analysis for detecting and correlating these biomarkers with sleep architecture. Results: Thirty-five patients were included in the study (9 MCI and 26 AD patients). 18 F-FDG uptake in left Brodmann area 31 (owing to the posterior cingulate cortex) correlated negatively with REM sleep latency (p = 0.013) and positively with REM sleep (p = 0.033). 18 F-FDG uptake in the hippocampus was negatively associated with sleep onset latency (p = 0.041). Higher CSF orexin levels were associated with higher sleep onset latency (p = 0.042), Non-REM stage 1 of sleep (p = 0.031), wake after sleep onset (p = 0.028), and lower sleep efficiency (p = 0.045). CSF levels of A 42 correlated negatively with the wake bouts index (p = 0.002). CSF total-tau and phosphorylated tau levels correlated positively with total sleep time (p = 0.045) and time in bed (p = 0.031), respectively. Conclusion: Sleep impairment, namely sleep fragmentation, REM sleep dysregulation, and difficulty in initiating sleep correlates with AD biomarkers, suggesting an effect of sleep on the pathological processes in different AD stages. Targeting sleep for counteracting the AD pathological processes represents a timely need for clinicians and researchers.
Investigative Ophthalmology & Visual Science, Apr 22, 2011
Purpose: : Several studies have shown that patients with Alzheimer’s Disease (AD) have a signific... more Purpose: : Several studies have shown that patients with Alzheimer’s Disease (AD) have a significantly increased rate of glaucoma occurrence. The purpose of the study was to evaluate the frequency of glaucoma and changes of the optic nerve head (ONH) morphology and/or retinal nerve fiber layer (RNFL) thickness in patients with AD. Methods: : 94 eyes of AD subjects and 127 eyes from age-matched controls underwent a complete eye examination including measurements of IOP, central corneal thickness and visual field testing using a Matrix FDT. ONH and RNFL assessment was performed both by slit lamp biomicroscopy and HRT III examination. The diagnosis of glaucoma was based on the presence of at least two of the following criteria: visual field defects characteristic of or compatible with glaucoma, specific ONH alterations and/or changes of HRT parameters. Results: : The Glaucoma Probability Score and Moorfields Regression Analysis (Mann Whitney U test: 0,004 and 0,001, respectively) and HRT3 stereometric parameters Rim Vol, RNFL thickness (ANOVA Tests of Between-Subjects Effects: 0,039 and 0,001, respectively) resulted significantly different along with the Matrix parameters MD (ANOVA: 0,001), PSD and GHT (Mann Whitney U test: 0,001 and 0,001 respectively) in patients with AD compared to the controls. The IOP mean value resulted to be significantly reduced (ANOVA: 0,001) in AD compared to controls. The frequency of glaucoma in AD patients (25,5 %) was significantly higher than in control group (5,5%) (p= 0.001). Conclusions: : The study confirmed that patients with AD have a higher frequency of glaucoma in the absence of elevated IOP levels. HRT III seems to be an useful tool in detecting ONH and RNFL changes in AD patients.
PubMed, Nov 1, 1989
We have studied Mongolian gerbils using somatosensory evoked potentials (SEP) recordings before, ... more We have studied Mongolian gerbils using somatosensory evoked potentials (SEP) recordings before, during and after an ischemic event. In six experimental animals, cerebral ischemia was reproduced by clamping both carotid arteries for ten minutes. Two recordings were made during this period at 4' and 8'. An additional four recordings were made after removal of the clamp at 4', 8', 12' and 20'. Four animals were utilized as a control group, and were subjected to the identical experimental protocol, with the exclusion of carotid artery clamping. During ischemia we observed an evident alteration of the SEP recordings in the experimental animals, and a more or less rapid recovery during the post-ischemic period. This experimental model may be useful for the monitoring and the evaluation of the evolution of cerebro-vascular damage during the post-ischemic period.
Multiple Sclerosis Journal, Aug 16, 2012
Dear Sirs, Although the origin of MS remains elusive, several studies have focused on different g... more Dear Sirs, Although the origin of MS remains elusive, several studies have focused on different genetic-environmental factors; in particular, the role of Epstein–Barr Virus (EBV) infection and virus-triggered immunopathology have been investigated.1–2 We report on a 64-year-old male presenting with fever, lethargy, stiff neck, left-trigeminal and right-facial nerves deficit, astasia, sensory loss in lower limbs, hypotonic and areflexic paraparesis. CSF analysis showed lymphocytic and mononuclear pleocytosis, amplifiable EBVDNA and EBV IgM and IgG. Brain MRI was unremarkable; spinal MRI showed a diffuse T2-weighted high-signal intensity (T2HSI) along the thoracic cord with gadolinium enhancement, and lumbosacral impingement of nerve roots and meninges. The patient achieved a full recovery after intravenous (i.v.) therapy with acyclovir 10 mg/kg t.i.d. and methylprednisolone 1000 mg/day. Combined clinical, CSF and MRI findings led to the diagnosis of encephalomyelomeningoradiculitis related to EBV infection. After a long period of total well-being, the patient presented two acute episodes of lower limbs sensory-motor deficit and severe sphinteric retention. The episodes were separated by a considerable time and each was followed by almost complete recovery. Neurological examination showed in both episodes brisk tendon reflexes in the lower limbs, bilateral Babinski sign and clonus in Achilles tendon reflexes. On both occasions normal cell count and mild increment of protein, lactate and IgG were detected in the CSF, but intrathecal synthesis of oligoclonal bands (OCBs) was unexpectedly evident at the immunoelectrofocusing. Virology from CSF and serum, as vasculitic and rheumatological screens, was negative. Brain and spinal MRI documented the progressive increment in size and number of T2HSI lesions, not evident previously. Somatosensory and visual evoked potentials (SEPs; VEPs) showed bilateral delay of the P40, N20 and P100 waves. In both episodes, a five-day treatment with i.v. methylprednisolone 1000 mg/day produced a full recovery, except for a residual numbness in the feet and sphinteric retention. Therefore, episodes were notably associated to: i) neuraxis-MRI documenting the progressive dissemination in time and space of the white matter lesions; ii) CSF intrathecal synthesis of OCBs; iii) altered evoked potentials; iv) response to i.v. corticosteroids. On this evidence the diagnosis of a demyelinating process occurring after an EBV neuraxis infection was postulated. MS aetiology is still unknown, but one of the most interesting conjectures is that MS may be primed and perpetuated by a neurotropic agent, possibly a virus, in genetically susceptible subjects, suggesting that a virus may initiate or trigger immunopathological demyelinating processes.1 Different neurotropic viruses have been variously invoked as the possible cause of MS and EBV is considered the outstanding candidate.2 In fact, there is ample documentation that a history of symptomatic primary EBV infection increases the risk of developing MS; moreover, it has been recently hypothesized that EBV can promote inflammatory processes by activating innate immune responses, for example IFNα production,3 although these data are still debated.4 The present case documents a clear relationship between an EBV-CNS infection and the subsequent development of a CNS demyelinating process, probably due to an immunological cross-reaction, showing clinical and paraclinical features in agreement with the McDonald criteria for MS diagnosis.5 Hence, we propose that EBV should be considered as playing a possible crucial role as a trigger in the pathogenesis of demyelinating processes.
Muscle & Nerve, Nov 1, 1995
A complete survey of the immunofluorescence distribution of the cytoskeletal protein vinculin in ... more A complete survey of the immunofluorescence distribution of the cytoskeletal protein vinculin in the normal skeletal muscle and peripheral nerve of humans and of different rodent species was performed. Our results enable us to localize vinculin in different types of adhesion plaques such as sarcolemmal costameres and neuromuscular and myotendinous junctions, but also in a fine intermyofibrillar lattice, possibly associated with intermediate filaments and/or with the triads. Moreover, we describe the presence of vinculin in junctional domains of several, previously unrecognized, specialized cells such as: the outer sheath of the muscle spindle capsule, the multilayered flat cells of the perineurium, the smooth muscle cells of epineurial blood vessels, and the endothelial cells in the endoneurium. These data call for a major role of vinculin in mechanisms of adhesion between cells, between cell and substrate and between intermyofibrillar components in the neuromuscular system. Such knowledge provides an anatomical background for studies on the possible pathological effects induced by an impairment in vinculin function.
Alzheimer Disease & Associated Disorders, Jul 1, 2013
Here we investigated the effect of the rivastigmine patch alone on depression in 50 mild Alzheime... more Here we investigated the effect of the rivastigmine patch alone on depression in 50 mild Alzheimer's disease (AD) patients with comorbid major depressive episode (MDE). First diagnosis acetyl-cholinesterase inhibitor and psychoactive drug-free outpatients (n=50) were recruited in memory clinics and reassessed after 3 and 6 months. Global cognitive functioning, depressive symptoms and MDE frequency were evaluated with the Mini Mental State Examination, the CERAD Dysphoria scale and the modified DSM-IV criteria for MDE in AD. MDE frequency reduced significantly from the first diagnostic visit (100%) to the 6-month follow-up (62%). We also found a significant reduction in CERAD Dysphoria scores that decreased from 6.2±3.9 mean±standard deviation to 4.9±4.5 at the 6-month follow-up. In AD patients with MDE rivastigmine alone can have a positive impact on depressive phenomena. Thus, future controlled study are justified to definitively verify if rivastigmine alone may improve depression in AD.
Epilepsia, Oct 1, 1995
Oxcarbazepine (OCBZ) is the keto-analogue of carbamazepine (CBZ). In humans, OCBZ is rapidly and ... more Oxcarbazepine (OCBZ) is the keto-analogue of carbamazepine (CBZ). In humans, OCBZ is rapidly and almost completely metabolized to 10, 11-dihydro-10-hydroxy-CBZ (GP 47779), the main metabolite responsible for the drug's antiepileptic activity. The corticostriatal pathway is involved in the propagation of epileptic discharges. We characterized the electrophysiological effects of GP 47779 on striatal neurons by making intracellular recordings from corticostriatal slices. GP 47779 (3-100 microM) produced a dose-dependent inhibition of glutamatergic excitatory postsynaptic potentials (EPSPs). This effect was not coupled either with changes of the membrane potential of these cells or with alterations of their postsynaptic sensitivity to excitatory amino acids (EAA) suggesting a presynaptic site of action. GP 47779 reduced the current-evoked firing discharge only at concentrations > 100 microM. GP 47779 did not affect the presynaptic inhibitory action of adenosine, showing that presynaptic adenosine receptors were not implicated in the GP 47779-mediated reduction of corticostriatal EPSPs. Our data indicate that GP 47779 apparently acts directly on corticostriatal terminals to reduce the release of EAA, probably by inhibiting high-voltage-activated (HVA) calcium (Ca2+) currents (described in the accompanying article). The inhibitory action of GP 47779 on corticostriatal transmission may contribute to the antiepileptic effects of this drug.
Neurology, Jun 26, 2006
To investigate if Helicobacter pylori (HP) eradication could make an effective and long-lasting i... more To investigate if Helicobacter pylori (HP) eradication could make an effective and long-lasting improvement in the pharmacokinetic and clinical response to l-dopa in patients with Parkinson disease (PD) and motor fluctuations. In a group of 34 HP-infected, motor-fluctuating patients with PD, the short-term (1-week) and long-term (3-month) beneficial effect of HP eradication (n = 17) was investigated in a double-blind fashion in comparison with a generic antioxidant treatment (n = 17), by means of pharmacokinetic, clinical, and gastrointestinal assessments. Results were compared with placebo treatment. Differently from the antioxidant-treated patients, the HP-eradicated patients showed a significant increase of l-dopa absorption, which was coupled with a significant improvement of clinical disability and with a prolonged "on-time" duration, whereas gastritis/duodenitis scores significantly decreased in line with a better l-dopa pharmacokinetics. These data demonstrate a reversible Helicobacter pylori (HP)-induced interference with l-dopa clinical response related to the impaired drug absorption, probably due to active gastroduodenitis. Therefore, the authors suggest that HP eradication may improve the clinical status of infected patients with Parkinson disease and motor fluctuations by modifying l-dopa pharmacokinetics.
Neuromuscular Disorders, Mar 1, 1996
Neurology, 2006
OBJECTIVE: To investigate if Helicobacter pylori (HP) eradication could make an effective and lon... more OBJECTIVE: To investigate if Helicobacter pylori (HP) eradication could make an effective and long-lasting improvement in the pharmacokinetic and clinical response to l-dopa in patients with Parkinson disease (PD) and motor fluctuations. METHODS: In a group of 34 HP-infected, motor-fluctuating patients with PD, the short-term (1-week) and long-term (3-month) beneficial effect of HP eradication (n = 17) was investigated in a double-blind fashion in comparison with a generic antioxidant treatment (n = 17), by means of pharmacokinetic, clinical, and gastrointestinal assessments. Results were compared with placebo treatment. RESULTS: Differently from the antioxidant-treated patients, the HP-eradicated patients showed a significant increase of l-dopa absorption, which was coupled with a significant improvement of clinical disability and with a prolonged "on-time" duration, whereas gastritis/duodenitis scores significantly decreased in line with a better l-dopa pharmacokinetics. CONCLUSIONS: These data demonstrate a reversible Helicobacter pylori (HP)-induced interference with l-dopa clinical response related to the impaired drug absorption, probably due to active gastroduodenitis. Therefore, the authors suggest that HP eradication may improve the clinical status of infected patients with Parkinson disease and motor fluctuations by modifying l-dopa pharmacokinetics
CHAPTER 17 Manganese Toxicity: A Critical Reappraisal Patrizia Vernole, Maria Morello, Giuseppe S... more CHAPTER 17 Manganese Toxicity: A Critical Reappraisal Patrizia Vernole, Maria Morello, Giuseppe Sancesario, Alessandro Martorana, Giorgio Bernard!, Antonella Canini, Palma Mattioli ABSTRACT Manganese is ... 1991; Jouve et al., 1975; Kimes and Morris, 1973; Mullen et al ...
PubMed, 2005
Twenty-six metals and the oxidative status in 71 patients affected by Parkinson's disease and 44 ... more Twenty-six metals and the oxidative status in 71 patients affected by Parkinson's disease and 44 healthy individuals were compared in order to identify potential biomarkers of the disease. In the patients, the following significant imbalances were found (p < or = 0.05): i) in serum, an increment of Ca, Mg, Ni, Si and V, and a decrement of Cd, Co, Fe, Li, Sn, Zn and Zr; ii) in blood, raised levels of Co, Li, Ni and Si and decreased of Al, Be, Ca, Cd, Fe, Mg, Mo, Sn, Zn and Zr; iii) increased formation of oxidant species and lowered anti-oxidant capacity (p < or = 0.001 for both). Barium, Bi, Cr, Cu, Hg, Mn, Pb, Sb, Sr, Tl and W did not change with the disease. The best discriminating variables between patients and controls were Cd, Co, Fe, Ni and Si in serum (91.2% of cases correctly classified), and Al, Cd, Co, Fe, Mo and Si in blood (98.2% of cases properly classified).
Cns & Neurological Disorders-drug Targets, Jun 1, 2013
Biosensors and Bioelectronics, Oct 1, 2020
In the overall scenario of precision medicine, we propose a novel paper-based lab-on-a-chip to de... more In the overall scenario of precision medicine, we propose a novel paper-based lab-on-a-chip to deliver a cost-effective and easy to use sensing tool for customized administration of drugs in Alzheimer's disease. Among several drugs, we designed the device for evaluating the efficacy of compounds (e.g. physostigmine, rivastigmine, donepezil) which are able to inhibit in a reversible way the cholinesterase enzyme. Because cholinesterase activity is peculiar to each patient, the administration of customized amount of the drug can improve the treatment efficacy and the quality of patient life, avoiding side effects due to the overdosage. In detail, we exploited Vivid™ Plasma Separation membrane to threat the whole blood sample, filter paper to load the reagents needed for the measurement, and office paper to print electrodes able to measure the butyrylcholinesterase activity, delivering a reagent free analytical tool. The calibration curve of butyrylcholinesterase obtained in blood sample provided linearity between 2 and 12 U/mL, with sensitivity of 0.050 ± 0.004 μA mL/U. The physostigmine, rivastigmine, and donepezil inhibition activities toward the butyrylcholinesterase enzyme were also measured in blood sample with linearity up to respectively 0.5 μM, 25 μM, 30 μM, and detection limits of 0.009 μM, 0.4 μM, 0.3 μM. These results demonstrate the capability of paper-based origami sensors as point of care devices to customize the drug administration in Alzheimer's disease.
Journal of the Neurological Sciences, Oct 1, 2006
Involvement of metals in the risk of developing Parkinson&amp;amp;#39;s disease (PD) has been... more Involvement of metals in the risk of developing Parkinson&amp;amp;#39;s disease (PD) has been suggested. In the present study, concentration of metals in cerebrospinal fluid (CSF), blood, serum, urine and hair of 91 PD patients and 18 controls were compared. Blood and hair were microwave digested, while CSF, serum and urine were water-diluted. Elements quantification was achieved by Inductively Coupled Plasma Atomic Emission Spectrometry and Sector Field Inductively Coupled Plasma Mass Spectrometry. Some metal imbalances in PD were observed: i), in CSF, lower Fe and Si; ii), in blood, higher Ca, Cu, Fe, Mg and Zn; iii), in serum, lower Al and Cu; iv), in urine, lower Al and Mn, higher Ca and Fe; and v), in hair, lower Fe. The ROC analysis suggested that blood Ca, Fe, Mg and Zn were the best discriminators between PD and controls. In addition, hair Ca and Mg were at least 1.5 times higher in females than in males of patients and controls. A decrement with age of patients in hair and urine Ca and, with less extent, in urine Si was observed. Magnesium concentration in CSF decreased with the duration and severity of the disease. Elements were not influenced by the type of antiparkinsonian therapy. Variation in elements with the disease do not exclude their involvement in the neurodegeneration of PD.
Brain, 1993
Unilateral 6-hydroxydopamine-induced lesions of the substantia nigra have been used as an experim... more Unilateral 6-hydroxydopamine-induced lesions of the substantia nigra have been used as an experimental model for Parkinson&#39;s disease. Although the biochemical and the behavioural effects of striatal denervation have been widely characterized, the physiological and pharmacological changes caused by dopamine depletion at the cellular level are still unknown. We studied the electrical activity of single rat striatal neurons recorded intracellularly in vitro from a brain slice preparation. Recordings were obtained at different periods after the denervation (4, 6, 8 months). In dopamine-denervated slices, unlike naive slices, most of the neurons showed spontaneous depolarizing postsynaptic potentials. The percentage of cells showing spontaneous depolarizing postsynaptic potentials was maximal 4 months after the denervation. In most of the dopamine-denervated neurons (60%) spontaneous depolarizing postsynaptic potentials were reversibly blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), an antagonist of non-N-methyl-D-aspartate glutamate receptors. In some neurons, however, the amplitude of spontaneous depolarizing postsynaptic potentials was reduced by bicuculline (30 microM) suggesting that they were mediated by the release of endogenous gamma-aminobutyric acid (GABA). Intrinsic membrane properties (membrane potential, input resistance and firing pattern) and postsynaptic responses to different agonists of excitatory amino acid receptors were not altered in neurons recorded from dopamine-depleted slices. In dopamine-depleted slices, unlike in naive slices, LY 171555 (0.1-10 microM), a D2 dopamine receptor agonist, reduced the frequency and the amplitude of CNQX-sensitive spontaneous depolarizing postsynaptic potentials and reduced the amplitude of glutamate-mediated synaptic potentials evoked by cortical stimulation. LY 171555 did not affect the membrane responses to exogenous glutamate. SKF 38393 (3 microM), a D1 dopamine receptor agonist, decreased postsynaptic excitability of striatal neurons recorded from naive animals. On the contrary, this agonist was ineffective in most of the cells obtained from dopamine-depleted slices. These results suggest that dopamine-denervation augments neuronal excitability in the striatum. Abnormal excitability of striatal neurons is not caused by changes of the intrinsic membrane properties of these cells, but is the result of increased glutamatergic cortical inputs to the striatum. Dopamine-denervation also alters the physiological responses to dopamine receptor stimulation. Nigral lesions induce supersensitivity of D2 dopamine receptors controlling the release of glutamate and reduce the inhibitory influence of D1 receptors at postsynaptic level. These functional changes of the striatal neurons may alter the output signals from the striatum to the other structures of the basal ganglia and then produce most of the physiopathological changes observed in Parkinson&#39;s disease.
Progress in Neurobiology, Jun 1, 2000
Striatal neurones receive myriad of synaptic inputs originating from dierent sources. Massive aer... more Striatal neurones receive myriad of synaptic inputs originating from dierent sources. Massive aerents from all areas of the cortex and the thalamus represent the most important source of excitatory amino acids, whereas the nigrostriatal pathway and intrinsic circuits provide the striatum with dopamine, acetylcholine, GABA, nitric oxide and adenosine. All these neurotransmitter systems interact each other and with voltage-dependent conductances to regulate the ecacy of the synaptic transmission within this nucleus. The integrative action exerted by striatal projection neurones on this converging information dictates the ®nal output of the striatum to the other basal ganglia structures. Recent morphological, immunohistochemical and electrophysiological ®ndings demonstrated that the striatum also contains dierent interneurones, whose role in physiological and pathological conditions represents an intriguing challenge in these years. The use of the in vitro brain slice preparation has allowed not only the detailed investigation of the direct pre-and postsynaptic electrophysiological actions of several neurotransmitters in striatal neurones, but also the understanding of their role in two dierent forms of corticostriatal synaptic plasticity, long-term depression and long-term potentiation. These long-lasting changes in the ecacy of excitatory transmission have been proposed to represent the cellular basis of some forms of motor learning and are altered in animal models of human basal ganglia disorders, such as Parkinson's disease. The striatum also expresses high sensitivity to hypoxic±aglycemic insults. During these pathological conditions, striatal synaptic transmission is altered depending on presynaptic inhibition of transmitter release and opposite membrane potential changes occur in projection neurones and in cholinergic interneurones. These ionic
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Papers by Giuseppe Sancesario