Biomedical subjects

A Peppe

Publications and source records attributed to A Peppe.

At least 19 recordsLinked to original sources

PubMed2006

Deep brain stimulation in Parkinson's disease patients: biochemical evidence.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) patients augments STN-driven excitation of the internal globus pallidus (GPi). However, other DBS-induced changes are largely unknown. Here we report the biochemical effects of STN-DBS in two basal ganglia stations (putamen--PUT--and GPi) and in a thalamic relay nucleus, the anteroventral thalamus (VA). In six advanced PD patients undergoing surgery, microdialysis samples were collected from GPi, PUT and VA before, during and after one hour of STN-DBS. cGMP was measured in the GPi and PUT as an index of glutamatergic transmission, whereas GABA was measured in the VA. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in the VA (-25%). Simultaneously, cGMP extracellular concentrations were enhanced in the PUT (+200%) and GPi (+481%). DBS differentially affects fibers crossing the STN area: it activates the STN-GPi pathway while inhibiting the GPi-VA one. These findings support a thalamic dis-inhibition, as the main responsible for the clinical effect of STN-DBS. This, in turn, re-establishes a more physiological level of PUT activity.

Aged↗

PubMed2006

Alexithymia in Parkinson's disease is related to severity of depressive symptoms.

The authors investigated the possible relationship between depression and alexithymia in a population of hospitalized patients suffering from Parkinson's disease (PD). Fifty-eight PD patients without dementia participated in the study. Alexithymia was screened using the 20 item version of the Toronto Alexithymia Scale (TAS 20). Depression was diagnosed using a Structured Clinical Interview (SCID I) for DSM-IV. Severity of depression was evaluated with the Beck Depression Inventory (BDI). The prevalence of Alexithymia was about 21%. PD patients with major depression were significantly more alexithymic (TAS 20 average score = 61.4) than PD patients without depression (TAS 20 average score = 47.4) and, also, tended to be more alexithymic than PD patients with minor depression (MiD; TAS 20 average score =50.6), whereas no difference was found between PD patients with MiD and PD patients without depression. Moreover, high scores obtained on the BDI were found to strongly predict high level of alexithymia in these patients. These results extend to a cohort of PD patients previous data from the literature evidencing a strong association between alexithymia and severity of depressive symptoms.

Affective Symptoms↗

PubMed2006

Major and minor depression in Parkinson's disease: a neuropsychological investigation.

Previous studies have failed to distinguish the differential contribution of major and minor depression to cognitive impairment in patients with idiopathic Parkinson's disease (PD). This study was aimed at investigating the relationships among major depression (MD), minor depression (MiD) and neuropsychological deficits in PD. Eighty-three patients suffering from PD participated in the study. MD and MiD were diagnosed by means of a structured interview (SCID-I) based on the DSM-IV criteria, and severity of depression was evaluated by the Beck Depression Inventory. For the neuropsychological assessment, we used standardized scales that measure verbal and visual episodic memory, working memory, executive functions, abstract reasoning and visual-spatial and language abilities. MD patients performed worse than PD patients without depression on two long-term verbal episodic memory tasks, on an abstract reasoning task and on three measures of executive functioning. The MiD patients' performances on the same tests fell between those of the other two groups of PD patients but did not show significant differences. Our results indicate that MD in PD is associated with a qualitatively specific neuropsychological profile that may be related to an alteration of prefrontal and limbic cortical areas. Moreover, the same data suggest that in these patients MiD and MD may represent a gradual continuum associated with increasing cognitive deficits.

Aged↗

PubMed2005

rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease.

The neural mechanisms and circuitry involved in levodopa-induced dyskinesia are unclear. Using repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) in a group of patients with advanced Parkinson disease, the authors investigated whether modulation of SMA excitability may result in a modification of a dyskinetic state induced by continuous apomorphine infusion. rTMS at 1 Hz was observed to markedly reduce drug-induced dyskinesias, whereas 5-Hz rTMS induced a slight but not significant increase.

Aged↗

PubMed2004

Pergolide effect on cognitive functions in early-mild Parkinson's disease.

In the present study, we evaluated the effect of pergolide, a mixed D1/D2 agonist, on cognitive function in mild Parkinson's disease (PD). After a two-week wash-out phase, twenty patients with a Hoehn and Yahr score </=2.5 entered a 16-week, cross-over study in which the order of administration of pergolide or 1-dopa was randomly assigned. Cognitive assessment was performed after the wash-out phase and repeated after eight weeks (before patients were switched to the other drug) and at the end of the study. There were no significant differences in test scores among the three experimental modalities (off-treatment vs. l-dopa, off-treatment vs. pergolide, pergolide vs. l-dopa). In another cohort of comparably mild PD patients we had previously demonstrated that pramipexole, a mixed D2/D3 agonist, slightly but significantly worsened verbal fluency in comparison to l-dopa; moreover, pramipexole impaired short term verbal memory and attentional-executive functions in comparison to both l-dopa and the off-treatment condition. Taken together, these findings suggest that dopamine agonists may influence cognition in PD according to their pharmacological characteristics. Unlike the D2/D3 agonist pramipexole, pergolide and l-dopa, both of which stimulate D1- and D2-receptor subtypes, do not appear to impair cognitive function.

Aged↗

PubMed2004

Time interval of oral feeding recovery as a prognostic factor in severe traumatic brain injury.

PRIMARY OBJECTIVES: To assess the outcome of severe traumatic brain injury at least 1 year after trauma, in relation to some early clinical prognostic factors occurring during coma recovery. RESEARCH DESIGN: Retrospective study conducted at the post-coma unit of a rehabilitation hospital. METHODS AND PROCEDURES: A total of 43 patients were included. All of the patients sustained severe traumatic brain injury and prolonged coma, i.e. coma lasting at least 15 days. Outcome was assessed by means of Glasgow Coma Scale, Barthel Index and Mini Mental State 1 year after trauma, in relation to some early clinical prognostic factors occurring during coma recovery. MAIN OUTCOMES AND RESULTS: At the 1 year follow-up, a statistically significant correlation was found with both the Glasgow Outcome Scale and the Barthel Index for the time interval from brain injury to recovery of the following clinical variables: optical fixation, ability to obey commands, spontaneous motor activity and first safe oral feeding. Psychomotor agitation and bulimia were also favourable prognostic factors for the final outcome. CONCLUSIONS: In the present study, first safe oral feeding during coma recovery represents the clinical feature that better predicts the final outcome of patients with severe traumatic brain injury and prolonged coma.

Adolescent↗

PubMed2004

Delayed administration may improve entacapone effects in parkinsonian patients non-responding to the drug.

BACKGROUND: Entacapone is a COMT inhibitor used in Parkinson's disease (PD) patients, as an adjunctive therapy to L-dopa in order to prolong its bioavailability and thus its clinical effect. However, previous studies reported entacapone-induced L-dopa to have lower C(max) and delayed t(max) values, coupled with a delayed onset of the clinical effect, possibly suggesting an interference between the two drugs. The aim of our study was to evaluate whether a delayed entacapone administration in association with standard L-dopa/carbidopa, may in some subjects improve the entacapone effects on L-dopa AUC and thus on the clinical 'on time' duration. METHODS: Twenty-eight idiopathic advanced PD patients were blindly evaluated in three different test days, following administration of carbidopa/L-dopa or carbidopa/L-dopa plus co-administered entacapone or plus entacapone administered with 30 min of delay. RESULTS: The AUC, the 'on time' and UPDRS score of the whole group were improved by both modalities of entacapone administration. An ex post analysis showed that the delayed entacapone administration produced a significant improvement in a subgroup of 10 non-responding patients to the co-administration. CONCLUSION: We suggest that the delayed administration should be attempted in the subjects not improved by entacapone co-administration.

Aged↗

PubMed2003

Pramipexole in comparison to l-dopa: a neuropsychological study.

Twenty right-handed patients affected by early/mild Parkinson's disease were evaluated in a randomised study using neuropsychological and clinical assessements during three treatment modalities: when in the off treatment condition, when on pramipexole, and when on l-dopa. In comparison to the off treatment condition, the DA-agonist pramipexole produced a significant impairment of short term verbal memory, attentional-executive functions and verbal fluency, while l-dopa did not. Moreover, pramipexole opposite to l-dopa, failed to improve FAS and Stroop tests. Present findings indicate that pramipexole may worsen cognitive functions although not exceeding normative values.

Aged↗

PubMed2002

Emotional processing in Parkinson's disease. A study using functional transcranial doppler sonography.

This study evaluated the use of transcranial Doppler ultrasonography for detecting selective changes in cerebral blood flow velocity during emotional processes. The aim was to investigate the possibility of obtaining functional information on the neuropsychology of emotions in patients with Parkinson's disease (PD). For this reason, blood flow velocity changes were investigated in both middle cerebral arteries (MCA) during a rest condition and when viewing non emotional (tasks 1 and 3) and emotional (task 2) slide sequences. The study included 12 PD patients and 12 healthy subjects. All patients were in treatment with levodopa or dopamine agonist. Investigation of PD patients was performed during an on-phase. The three tasks produced significantly different effects on the right and left side in the PD patients compared with the control group. During the two non emotion-related tasks the increase of mean flow velocity (MFV) compared with the basal values was similar in the two middle cerebral arteries in both groups [(PD Patients: Task 1: left MCA = 3.95 % 2.2, Right MCA = 4.33 % +/- 2.3, Task 3: left MCA = 3.04 % +/- 1.9, Right MCA = 2.71 % +/- 2.2) (control group: Task 1: left MCA = 4.57 % +/- 1.4, Right MCA = 4.46 % +/- 1.7, Task 3: left MCA = 2.32 % +/- 0.9, Right MCA = 2.52 % +/- 1.2)] The negative emotional task was accompanied by a significantly higher increase in the right (10.53 % +/- 3.2) than in the left middle cerebral artery (4.52 % +/- 1.51) only in the control group. The PD patients showed a bilateral and symmetrical increase of MFV (left MCA = 4.28 % +/- 2.3 and right MCA 5.77 % +/-3.8). To determine whether there was a dysfunction in cerebrovascular reactivity and a deficit in the ability to activate both hemispheres in response to non emotion-related stimuli in the PD patients, the protocol study included a cerebrovascular reactivity test to apnea, a motor task (thumb-to-finger opposition), a cognitive task (word fluency and visual discrimination of objects), performed by both patients and controls. The pattern of MFV changes during these tasks was not statistically significantly different in the two experimental groups. In order to evaluate the possible influence of drug treatment on cerebrovascular reactivity, seven patients were also evaluated during an off-phase, after a 48-hour wash-out period. Changes in MFV during every task were similar to that observed during the on-phase. These findings show the possibility of obtaining specific functional information from bilateral transcranial Doppler and suggest the selective and specific deficit of PD patients in emotional processing.

Aged↗

PubMed2002

Subdyskinetic apomorphine responses in globus pallidus and subthalamus of parkinsonian patients: lack of clear evidence for the 'indirect pathway'.

OBJECTIVES: Previous studies suggested that the hypo-activity of the external pallidus (GPe) might drive the hyper-activity of subthalamic neurons, which underlies the cardinal symptoms of Parkinson's disease. We have challenged this view, based on the so-called 'indirect pathway', by recording apomorphine effects from both structures of parkinsonian patients, at rest and during passive movements. METHODS: We performed single-unit recordings from external pallidus (GPe), internal pallidus (GPi) and subthalamic nucleus (STN) during the stereotactic neurosurgery aimed to implant deep brain stimulating electrodes in GPi or STN. First, we verified the firing frequency of each structure in off-state conditions. Then, therapeutic, subdyskinetic concentrations of the dopaminergic agonist apomorphine was delivered to assess each nucleus response. RESULTS: The firing rate of STN averaged about 40 Hz; a large proportion (75%) of STN units exhibited marked responsiveness to passive movements. Apomorphine reduced the firing discharge of parkinsonian STN in all cells, although electrophysiological recovery was usually incomplete. Movement-related activity was also dramatically reduced. In contrast, apomorphine failed to modify the firing frequency of GPe, despite the amelioration of hypo-kinetic symptoms and the simultaneous inhibition of GPi firing discharge. CONCLUSIONS: We demonstrate that part of the models on basal ganglia circuitry needs to be revised. The re-balancing of STN hyper-activity, when patients benefit from dopaminergic therapy, is not due to an increased input from GPe, but, instead, due to changes in STN intrinsic firing properties and/or modulation of glutamatergic inputs.

Adult↗

PubMed2002

Deep brain stimulation of both subthalamic nucleus and internal globus pallidus restores intracortical inhibition in Parkinson's disease paralleling apomorphine effects: a paired magnetic stimulation study.

OBJECTIVE: We investigated the effect of bilateral subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) on intracortical inhibition (ICI) in patients with advanced Parkinson's disease (PD). METHODS: The activity of intracortical inhibitory circuits was studied in 4 PD patients implanted with stimulating electrodes both in STN and GPi by means of paired-pulse transcranial magnetic stimulation, delivered in a conditioning-test design at short (1-6 ms) interstimulus intervals (ISI). The effect of apomorphine on the same PD patients was also investigated. RESULTS: We observed that implanted PD patients showed a significant increase in ICI during either bilateral STN or GPi DBS at 3 ms ISI, and during bilateral STN DBS at 2 ms ISI in comparison to their off DBS condition. The same statistical improvement was observed during apomorphine infusion at 3 and 2 ms ISI. In each condition, the electrophysiological changes were associated with a significant clinical improvement as measured by the Unified Parkinson's Disease Rating Scale motor examination. CONCLUSIONS: These results are consistent with the hypothesis that basal ganglia DBS can mimic the effects of pharmacological dopaminergic therapy on PD patients cortical activity. We propose that in PD patients, the basal ganglia DBS-induced improvement of ICI may be related to a recovery in modulation of thalamo-cortical motor pathway.

Antiparkinson Agents↗

PubMed2001

Deep brain stimulation (DBS) attentional effects parallel those of l-dopa treatment.

Aim of our study was to investigate the different effects on attentional capacity of deep brain stimulation DBS (STN or GPi) and of l-dopa in PD patients. Patients were evaluated on-DBS/off-l-dopa, on-l-dopa/off-DBS, on-l-dopa/on-DBS and off-l-dopa/off-DBS. Our results indicate that DBS effects on attentional functions parallel those of l-dopa. A site independent (both STN and GPi) worsening of verbal fluency was observed, possibly connected to the stimulus effect on the cortico-subcortical-cortical loop.

Adult↗

PubMed2001

Bilateral GPi DBS is useful to reduce abnormal involuntary movements in advanced Parkinson's disease patients, but its action is related to modality and site of stimulation.

In Parkinson's disease (PD) patients, internal globus pallidus (GPi) stimulation has been reported to produce good effects on abnormal involuntary movements (AIM); less improvement has been observed in extrapyramidal symptoms. We assessed the effect of monopolar dorsal (uppermost), ventral (lowest) and bipolar (uppermost vs. lowest) bilateral globus pallidus stimulation by quadripolar electrode on extrapyramidal symptoms and AIM induced by a dose of apomorphine. Six PD patients were studied in OFF therapy condition after surgery without stimulation (STIM OFF) and during stimulation (STIM ON) with the three different modalities. All patients were evaluated by the unified Parkinson's disease rating scale, section III (UPDRS) and by the AIM. Our results show that all three bilateral GPi stimulation modalities reduce the UPDRS score (between 49.7 and 31.5%), although the bipolar and lowest stimulation are the most effective. Similarly, bipolar and lowest stimulation were also the most effective in reducing the occurrence and intensity of the apomorphine-induced AIM. On the contrary, uppermost stimulation (UP ON) produced an AIM occurrence similar to that observed in the OFF stimulus condition. We suggest that bilateral GPi stimulation is an useful procedure to ameliorate extrapyramidal signs of advanced PD patients; however, it produces an antidyskinetic effect only if the ventral or the entire GPi is stimulated. On the contrary, the UP ON, most probably located in the external globus pallidus (GPe), does not modify the AIM occurrence.

Aged↗

PubMed1999

Electrophysiological and clinical desensitization to apomorphine administration in parkinsonian patients undergoing stereotaxic neurosurgery.

A decreased motor response after repeated doses of apomorphine is observed in severely affected Parkinson's disease patients. We simultaneously studied clinical symptoms and internal pallidus single unit activity in three parkinsonian patients underlying stereotaxic neurosurgery for deep brain stimulation. In each patient, two closely spaced doses of intraoperatory apomorphine were administered, while recording the same extracellular unit. The reduced clinical effect of the second administration was correlated to a lessened inhibition of the pallidal single unit recorded throughout the double administration. Our data support the proposition that fast postsynaptic desensitization to dopamine agonists may take place in the basal ganglia nuclei and play a role in the physiopathology of levodopa long-term treatment syndrome.

Apomorphine↗

PubMed1999

Basal ganglia and gait control: apomorphine administration and internal pallidum stimulation in Parkinson's disease.

Gait coordination was analyzed (four-camera 100 Hz ELITE system) in two groups of idiopathic Parkinson disease (PD) patients. Five patients underwent continuous infusion of apomorphine and were recorded in two different sessions (APO OFF and APO ON) in the same day. Three patients with a previous chronic electrode implantation in both internal globi pallidi (GPi) were recorded in the same experimental session with the electrodes on and off (STIM ON and STIM OFF). The orientation of both the trunk and the lower-limb segments was described with respect to the vertical in the sagittal plane. Lower-limb inter-segmental coordination was evaluated by analyzing the co-variation between thigh, shank, and foot elevation angles by means of orthogonal planar regression. At least 30 gait cycles per experimental condition were processed. We found that the trunk was bent forward in STIM OFF, whereas it was better aligned with the vertical in STIM ON in both PD groups. The legs never fully extended during the gait cycle in STIM OFF, whereas they extended before heel strike in STIM ON. The multisegmental coordination of the lower limb changed almost in parallel with the changes in trunk orientation. In STIM OFF, both the shape and the spatial orientation of the planar gait loops (thigh angle vs. shank angle vs. foot angle) differed from those of physiological locomotion, whereas in STIM ON the gait loop tended to resume features closer to the control. Switching the electrodes on and off in patients with GPi electrodes resulted in quasi-parallel changes of the trunk inclination and of the planar gait loop. The bulk of the data suggest that the basal-ganglia circuitry may be relevant in locomotion by providing an appropriate spatio-temporal framework for the control of posture and movement in a gravity-based body-centered frame of reference. Pallido-thalamic and/or pallido-mesencephalic pathways may influence the timing of the inter-segmental coordination for gait.

Aged↗

PubMed1999

A mixed D1 and D2 antagonist does not replay pattern electroretinogram alterations observed with a selective D2 antagonist in normal humans: relationship with Parkinson's disease pattern electroretinogram alterations.

The human retina produces a tuned response to stimuli of increasing spatial frequency reversed at a steady state. The peak amplitude response, at medium spatial frequencies, is decreased in Parkinson's disease and in normal subjects (n = 18) treated with a D2 dopaminergic antagonist (l-sulpiride). Here, we report that a mixed D1-D2 receptor antagonist (haloperidol) in normal subjects (n = 18) does not produce an amplitude decrease of medium spatial frequencies (SFs) responses but it decreases low-frequency response. It could argued that the increased dopamine release produced by the presynaptic D2 antagonistic action of haloperidol is subsequently counteracted at postsynaptic level by its D1 antagonistic effect, producing a net counterbalance at medium SFs. These data suggest that the two dopamine receptors may play different roles in the retinal function and in the origin of visual alterations in Parkinson's disease.

Adult↗

PubMed1999

The effect of deep brain stimulation on the frontal N30 component of somatosensory evoked potentials in advanced Parkinson's disease patients.

OBJECTIVES: In the present study we investigated whether in advanced Parkinson's disease (PD) patients the frontal component of short somatosensory evoked potentials (SEPs) to median nerve stimulation may be modified by basal ganglia deep brain stimulation (DBS). METHODS: We recorded the SEPs in 6 PD patients undergoing bilateral functional neurosurgery in the internal globus pallidus (GPi) (4 patients) and in the nucleus subthalamicus (STN) (two patients) during ineffective and effective bilateral BDS. Pre-operatively, the SEPs were also recorded in off therapy and during apomorphine infusion. RESULTS: From the evaluation of the latency and the amplitude characteristics of the major parietal (N20 and P25) and frontal (N30) components, we observed that whereas the parietal waves did not vary in any condition, the N30 potential showed a remarkable amplitude increase during apomorphine as well as during effective bilateral GPi or STN DBS. Furthermore, after the stimulators were turned off we noticed that the N30 amplitude potential progressively faded almost in parallel with the attenuation of DBS clinical effects. CONCLUSIONS: Our results lead to the conclusion that the bilateral DBS of both GPi and STN is really effective in producing a selective increase of frontal N30 amplitude probably improving the supplementary motor area functional activity, but these results do not clarify whether this amelioration is due to a central or a 'long loop' mechanism.

Antiparkinson Agents↗

PubMed1999

Verbal working memory deficit in Parkinson's disease subjects.

The aim of the present work was to evaluate verbal working memory in patients affected by Parkinson's disease (PD). In particular, tests that explore the functionality of the Articulatory Loop and of the Central Executive during verbal tasks were given. PD patients displayed normal phonological similarity, word length and word frequency effects in a Word span task, thus demonstrating adequate retention capacity of the phonological store, normal functioning of the articulatory rehearsal mechanism and a normal contribution of lexical-semantic knowledge to verbal immediate recall. In the Brown-Peterson task, PD patients showed abnormal performance decay on the letter recall task when articulatory rehearsal was inhibited by a serial subtraction concurrent task. These data provide evidence for normal functioning of the Articulatory Loop in PD patients. However, when the verbal recall task is more attention demanding, PD patients show deficient performance levels, presumably due to depleted processing resources by the Central Executive.

Adult↗