-
[show abstract]
[hide abstract]
ABSTRACT: Dementia has become a relevant problem associated with the elderly in our countries. Increased interest in the field has yielded a copious literature, so far mostly centered on Alzheimer's dementia. Cerebrospinal fluid (CSF) analysis combined with neuropsychology, even in absence of neuroimaging, represents the gold standard to reach a diagnosis when cortical cognitive impairment prevails. In view of this, low levels of CSF amyloid peptides β (Aβ) and high tau/Aβ protein ratio, despite prominent impairment of executive functions or concomitant vascular burden, facilitate the diagnosis of Alzheimer's disease. Conversely, an early cognitive impairment occurring in patients suffering from Parkinson's disease (PD) or Lewy body disorders (LBDs), both diagnoses posed on pure clinical grounds, remains quite elusive in term of biomarkers or neuropsychological assessment. Whether PD with dementia (PDD) and dementia with Lewy bodies (DLB) represent further steps along with a continuum of the same progressive degeneration due to Lewy bodies deposition, rather then the association of Lewy bodies and Aβ pathology, remains a challenging issue. Aim of this work is to set a state-of-the-art on the neuropsychological profiles of both or DLB. Then, we will focus on the ongoing controversies about the specificity of the standard CSF biomarkers if applied to extrapyramidal disorders. Our conclusions are that the CSF pattern, in PDD and DLB, can certainly be distinct from that in AD, though mechanisms leading to dementia could be shared among them. It is possible that, by combining imaging tracers, neuropsychologically careful assessment and renewed CSF biomarkers, DLB can be better distinguished in subgroups, depending on the presence or absence of a relevant amyloid burden. However, more complete data, possibly collected in fieri during the progressive derangement of cognitive abilities, are needed to improve our ability to decipher and treat these entities.
Acta Neurovegetativa 05/2012; 119(7):861-75. · 2.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cerebellar repetitive transcranial magnetic stimulation may be effective in reducing peak-dose levodopa induced dyskinesia in Parkinson's disease patients. It was proposed that the antidyskinetic effect could be due to modulation of cerebello-thalamo-cortical pathways. However the neural basis for these clinical effects have not yet been demonstrated.
We investigated the effects of repeated sessions of cerebellar continuous theta burst stimulation in Parkinson's disease patients with levodopa induced dyskinesia on brain metabolism by means of positron emission tomography scan with fluorodeoxyglucose ((18)F-FDG) to characterize the specific cerebral network activated by cerebellar stimulation in these patients.
We found that five days of bilateral cerebellar continuous theta burst stimulation (cTBS) were effective in reducing levodopa induced dyskinesia. Clinical changes were paralleled by a reduction of (18)F-FDG metabolism in the cerebellum as revealed by positron emission tomography imaging. We found a global decrease in the metabolism of the bilateral cerebellar hemispheres, and a significant decrease in (18)F-FDG uptake in correspondence of bilateral dentate nucleus.
Our study demonstrates the antidyskinetic effect of cerebellar cTBS in Parkinson's disease patients with levodopa induced dyskinesia, is paralleled by modulation of the activity of the pathways connecting the cerebellar cortex with the deep cerebellar nuclei, confirming the hypothesis that the motor cerebellar circuit is involved in the generations of levodopa induced dyskinesia.
Parkinsonism & Related Disorders 09/2011; 18(1):59-62. · 3.80 Impact Factor
-
Elisa Iacovelli,
Francesca Gilio,
Giuseppe Meco,
Francesco Fattapposta,
Nicola Vanacore, Livia Brusa,
Elena Giacomelli,
Maria Gabriele,
Alfonso Rubino,
Nicoletta Locuratolo,
Cesare Iani,
Floriana Pichiorri,
Carlo Colosimo,
Antonio Carbone,
Giovanni Palleschi,
Maurizio Inghilleri
[show abstract]
[hide abstract]
ABSTRACT: In Parkinson's disease (PD) the urinary dysfunction manifests primarily with symptoms of overactive bladder (OAB). The OAB questionnaire (OAB-q) is a measure designed to assess the impact of OAB symptoms on health-related quality of life. In this study, we quantified the urinary symptoms in a large cohort of PD patients by using the OAB-q short form. Possible correlations between the OAB-q and clinical features were tested. Three hundred and two PD patients were enrolled in the study. Correlations between the OAB-q and sex, age, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), Hoehn-Yahr (H-Y) staging, disease duration, and treatment were analyzed. Data were compared with a large cohort of 303 age-matched healthy subjects. The OAB-q yielded significantly higher scores in PD patients than in healthy subjects. In the group of PD patients, all the variables tested were similar between men and women. Pearson's coefficient showed a significant correlation between mean age, disease duration, mean OAB-q scores, UPDRS-III scores, and H-Y staging. A multiple linear regression analysis showed that OAB-q values were significantly influenced by age and UPDRS-III. No statistical correlations were found between OAB-q scores and drug therapy or the equivalent levodopa dose, whilst the items relating to the nocturia symptoms were significantly associated with the equivalent levodopa dose. Our findings suggest that bladder dysfunction assessed by OAB-q mainly correlates with UPDRS-III scores for severity of motor impairment, possibly reflecting the known role of the decline in nigrostriatal dopaminergic function in bladder dysfunction associated with PD and patients' age. Our study also suggests that the OAB-q is a simple, easily administered test that can objectively evaluate bladder function in patients with PD.
Movement Disorders 03/2010; 25(9):1203-9. · 4.51 Impact Factor
-
Stefani Alessandro,
Roberto Ceravolo, Livia Brusa,
Mariangela Pierantozzi,
Alberto Costa,
Salvatore Galati,
Fabio Placidi,
Andrea Romigi,
Cesare Iani,
Francesco Marzetti,
Antonella Peppe
[show abstract]
[hide abstract]
ABSTRACT: Between 2005 and 2007, six patients affected by idiopathic Parkinson's disease (IPD) were submitted to the bilateral implantation (and subsequent deep brain stimulation — DBS) of the pedunculopontine nucleus (PPN) plus the subthalamic nucleus (STN). This review synthesizes the effects of PPN low-frequency stimulation on non-motor functions, focusing on patient sleep quality and cognitive performance. If not associated to STN-DBS, PPN-DBS promoted a modest amelioration of patient motor performance. However, during PPN-DBS, they experienced on the one hand a significant improvement in executive functions and working memory, on the other hand a beneficial change in sleep architecture. Overall, the limited sample hampers definite conclusions. Yet, although the PPN-DBS induced motor effects are quite disappointing (discouraging extended trials based upon the sole PPN implantation), the neuropsychological profile supports the contention by which in selected PD patients, with subtle cognitive deficits or vanished efficacy of previous implanted STN, PPN-DBS might still represent a reliable and compassionate option.
Journal of the Neurological Sciences 02/2010; · 2.35 Impact Factor
-
Alessandro Ferraris,
Tamara Ialongo,
Giulio Cesare Passali,
Maria Teresa Pellecchia, Livia Brusa,
Marianna Laruffa,
Arianna Guidubaldi,
Gaetano Paludetti,
Alberto Albanese,
Paolo Barone,
Bruno Dallapiccola,
Enza Maria Valente,
Anna Rita Bentivoglio
[show abstract]
[hide abstract]
ABSTRACT: Hyposmia is a common nonmotor feature of Parkinson's disease (PD) and has been variably detected in monogenic Parkinsonisms. To assess olfactory dysfunction in PINK1-related Parkinsonism, we evaluated olfactory detection threshold, odor discrimination, and odor identification in five groups of subjects: sporadic PD (n = 19), PINK1 homozygous (n = 7), and heterozygous (n = 6) parkinsonian patients, asymptomatic PINK1 heterozygous carriers (n = 12), and Italian healthy subjects (n = 67). All affected subjects and all healthy heterozygotes but one resulted hyposmic, with most patients in the range of functional anosmia or severe hyposmia. Detection threshold was more preserved and discrimination more impaired in patients with PINK1 mutations than in PD cases. Alterations of detection and discrimination were observed also in PINK1 asymptomatic heterozygotes. On the contrary, odor identification appeared to be mostly related to the disease status, as it was impaired in nearly all patients (including PD and PINK1 cases) and preserved in healthy heterozygotes. Our data indicate that olfactory dysfunction is common in PINK1 Parkinsonism and consists typically in defective odor identification and discrimination. A milder olfactory deficit, mostly involving discrimination, can be found in asymptomatic heterozygotes, possibly indicating an underlying preclinical neurodegenerative process.
Movement Disorders 11/2009; 24(16):2350-7. · 4.51 Impact Factor
-
Movement Disorders 09/2009; 24(13):2020-2. · 4.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Aripiprazole (AP), a dopamine (DA) D(2) receptor partial agonist, has recently been used to reduce schizophrenic symptoms, while tetrabenazine (TBZ), a DA depletor, has been used to treat hyperkinesias in Huntington's disease (HD). The aim of this study is to define the role of AP on chorea, motor performance, and functional disability, and to compare the effects of AP vs. TBZ in a small study of six patients with HD. Both AP and TBZ increased the Unified Huntington's Disease Rating Scale (UHDRS) chorea score in a similar way. However, AP caused less sedation and sleepiness than TBZ and was better tolerated by the patients on the trial. Moreover, AP showed a slight but not significant improvement of depression in the patients as compared to TBZ. A larger group of patients and a longer period of observation are an important prerequisite for further evaluations of AP's therapeutic use.
Movement Disorders 02/2009; 24(1):126-9. · 4.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Patients affected by Parkinson's disease (PD) may present with lower urinary tract (LUT) dysfunction characterized by involuntary detrusor overactivity. We evaluated possible impact of a 2-week course of low frequency 1 Hz repetitive transcranial magnetic stimulation (rTMS) on LUT behavior in eight advanced PD patients complaining of urinary disturbances. We tested the effects of rTMS measuring urodynamic examination and the International Prostate Symptoms Score (IPSS) questionnaire, used for evaluation of subjective LUTS. rTMS was able to improve temporarily LUT behavior in PD patients, increasing bladder capacity and the first sensation of filling phase. Moreover, a reduction of IPSS score was noticed, due to an improvement on filling phase symptoms. The beneficial effects assessed with the IPSS lasted for up to 2 weeks after the end of the stimulation. rTMS seems to be an effective, noninvasive alternative treatment for PD patients with urinary disturbances.
Movement Disorders 02/2009; 24(3):445-8. · 4.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Three decades of basic research have focused on the multiple functions sub-served by the pedunculopontine nucleus (PPN) in
mammals. Yet, far from understood is the impact that lesioning PPN or modulating PPN-fugal pathways have on motor, limbic
and/or associative domains. Recently, we have pioneered the low-frequency deep brain stimulation (DBS) of pontine tegmental
areas in severely parkinsonian patients, aiming at providing new insights in the knowledge of this puzzling region. Here we
show that, under PPN-DBS, significant amelioration of axial and hypokinetic signs occurs (although to a lesser extent than
following STN-DBS in the same patients), together with a normalization of the spinal H reflex. Furthermore, PPN-DBS improves
REM sleep behaviour disorder and attentive and cognitive executive performances.
As a first step to understand the limited motor response to PPN-DBS, systematic intra-operative recordings in STN were performed
during PPN-DBS at 25 Hz. Almost each STN cell showed significant and long-lasting changes of the mean firing frequency during
PPN stimulation. However, PPN-ON caused two conflicting effects: a dramatic decrease of the ongoing firing in bursting STN
neurons and a large excitatory effect in irregular and tonic neurons. If dampening of STN bursting units seems to be in accord
with the PPN therapeutic role, the simultaneous excitatory influence in non-bursting cells might counteract the efficacy on
motor signs.
As a further step to understand the mechanisms underlying non-motor benefits, FDG-PET imaging was routinely performed in different
conditions (PPN-OFF, PPN-ON). These investigations might clarify whether PPN-ON influences the subcortico-cortical pathways
responsible for learning processes and goal-directed behaviours. Preliminary data confirm the possibility that PPN-DBS affects
multiple ascending pathways involving intralaminar thalamic nuclei and the ventral tegmental area.
These findings confirm a complex interplay between PPN, basal ganglia and cortical regions. However, the size of the inserted
electrode, extension of the electrical field and inter-individual anatomical differences of the surgical targeting do not
allow us to draw any definite conclusions.
12/2008: pages 573-587;
-
Gianluigi Lunardi,
Salvatore Galati,
Domenicantonio Tropepi,
Vincenzo Moschella, Livia Brusa,
Mariangela Pierantozzi,
Alessandro Stefani,
Silvia Rossi,
Francesco Fornai,
Ernesto Fedele,
Paolo Stanzione,
Atticus H Hainsworth,
Antonio Pisani
[show abstract]
[hide abstract]
ABSTRACT: To assess possible differences in dopamine metabolism that could parallel disease progression in Parkinson's disease (PD), we measured dopamine (DA) and its metabolites in the cerebrospinal fluid (CSF) in PD patients at different stages of disease: de novo (DEN), advanced not showing dyskinesias (ADV), and advanced with dyskinesias (DYS). DA, homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) were significantly higher in DEN patients compared with other groups. A negative exponential correlation related DA level and disease duration. The HVA/DA ratio was significantly higher in the ADV and DYS group than that found in DEN group. Our data show that disease progression produces an early large decay of DA levels, followed by a stabilization. On the contrary, a late change in DA turnover (increased HVA/DA ratio) is documented in patients with longer disease duration. Our results suggest that the appearance of dyskinesia may not be related to a further loss of DA terminals but to a different, abnormal, DA turnover.
Parkinsonism & Related Disorders 12/2008; 15(5):383-9. · 3.80 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The present study was aimed at investigating the effect of acute levodopa administration on the performance of a group of individuals with Parkinson's disease (PD) on a time-based prospective memory task. Twenty PD patients and 15 healthy controls were administered a task that required executing three actions after 10 min had elapsed in three consecutive trials. Scores were computed for correct recall of the intention to perform the actions and for correct execution of the actions. PD participants were evaluated after a 12-hr drug wash-out in two conditions: (1) after levodopa administration ("on"); (2) without drug administration ("off"). In the "on" condition, PD patients were significantly more accurate in retrieving the intention to perform the actions than in the "off" condition and their performance was actually comparable to that of healthy controls. The increased accuracy in complying with the prospective memory task following levodopa medication supports the idea that dopamine depletion plays a role in the prospective memory deficits observed in PD patients.
Journal of the International Neuropsychological Society 08/2008; 14(4):601-10. · 2.76 Impact Factor
-
Mariangela Pierantozzi,
Maria Giuseppina Palmieri,
Salvatore Galati,
Paolo Stanzione,
Antonella Peppe,
Domenicantonio Tropepi, Livia Brusa,
Antonio Pisani,
Vincenzo Moschella,
Maria Grazia Marciani,
Paolo Mazzone,
Alessandro Stefani
[show abstract]
[hide abstract]
ABSTRACT: Bilateral peduncolopontine nucleus (PPN) and subthalamic nucleus (STN) deep brain stimulation (DBS) was performed in six-advanced Parkinson's disease (PD) patients. We report the effect of both PPN-DBS (25 Hz) and STN-DBS (185 Hz) on patient spinal reflex excitability by utilizing the soleus-Hoffman reflex (HR) threshold. Compared to controls (n = 9), patients showed an increase of HR-threshold, which was scarcely affected by levodopa, but significantly reduced by DBS. In particular, we found that PPN-DBS alone, or plus STN-DBS induced a complete recovery of HR-threshold up to control values. The HR-threshold changes, although do not allow to investigate the contribution of specific intraspinal pathways, suggest that PPN may play a key-role in modulating spinal excitability in PD possibly by improving the basal ganglia-brainstem descending system activity.
Acta Neurovegetativa 06/2008; 115(5):731-5. · 2.73 Impact Factor
-
Giacomo Koch,
Alberto Costa, Livia Brusa,
Antonella Peppe,
Ilaria Gatto,
Sara Torriero,
Emanuele Lo Gerfo,
Silvia Salerno,
Massimiliano Oliveri,
Giovanni Augusto Carlesimo,
Carlo Caltagirone
[show abstract]
[hide abstract]
ABSTRACT: The basal ganglia have been associated with temporal processing in ranges of milliseconds and seconds. However, results from PD patient studies are elusive. Time perception in these patients has been tested with different approaches including repetitive movement tasks (i.e. finger tapping) and cognitive tasks (i.e. time reproduction), and both abnormal and normal performances have been reported for different time intervals. Furthermore, when PD patients were required to learn two target durations in the same session when they were off medication, they overestimated the short duration and underestimated the long duration in the seconds range. This pattern of temporal accuracy was described as a "migration effect" and was interpreted as a dysfunctional representation of memory for time (Malapani, C., Rakitin, B. C., Levy, R., Meck, W. H., Deweer, B., Dubois, B., et al. (1998). Coupled temporal memories in Parkinson's disease: A dopamine-related dysfunction. Journal of Cognitive Neuroscience, 10, 316-331). Here, we controlled the emergence of similar behaviour also during millisecond time processing in PD patients. A time reproduction task was employed in which subjects were required to estimate intervals in millisecond (500ms) and few second (2000ms) ranges. In the first experiment, these intervals were tested in the same session to verify whether the migration effect was present also between time intervals in different millisecond and few second ranges. In a second experiment, they were not intermingled but were tested in two separate sessions to verify whether abnormalities depended on a selective perceptual deficit of the time intervals tested (i.e. millisecond or second ranges). All experiments were performed in both off and on therapy conditions. Our results demonstrated that PD patients showed no deficits in time estimation for time intervals in either the millisecond or few second range when the different time intervals were tested in separate sessions. This negative finding was obtained in both on and off conditions. However, when the different ranges were tested in the same session, we found that PD patients were impaired selectively for time intervals in the seconds range. Our data seem to indicate that time processing in PD patients for time intervals spanning up to 2s is unimpaired and that abnormalities in such temporal scale may emerge only when patients have to deal with different durations, when timing involves further cognitive processes such as memory and attention.
Neuropsychologia 05/2008; 46(5):1305-13. · 3.64 Impact Factor
-
Roberta Marongiu,
Alessandro Ferraris,
Tàmara Ialongo,
Silvia Michiorri,
Francesco Soleti,
Francesca Ferrari,
Antonio E Elia,
Daniele Ghezzi,
Alberto Albanese,
Maria Concetta Altavista, [......],
Cesa Scaglione,
Paolo Stanzione,
Michele Tinazzi,
Anna Zecchinelli,
Massimo Zeviani,
Emanuele Cassetta,
Barbara Garavaglia,
Bruno Dallapiccola,
Anna Rita Bentivoglio,
Enza Maria Valente
[show abstract]
[hide abstract]
ABSTRACT: Heterozygous rare variants in the PINK1 gene, as well as in other genes causing autosomal recessive parkinsonism, have been reported both in patients and healthy controls. Their pathogenic significance is uncertain, but they have been suggested to represent risk factors to develop Parkinson disease (PD). The few large studies that assessed the frequency of PINK1 heterozygotes in cases and controls yielded controversial results, and the phenotypic spectrum is largely unknown. We retrospectively analyzed the occurrence of PINK1 heterozygous rare variants in over 1100 sporadic and familial patients of all onset ages and in 400 controls. Twenty patients and 6 controls were heterozygous, with frequencies (1.8% vs. 1.5%) not significantly different in the two groups. Clinical features of heterozygotes were indistinguishable to those of wild-type patients, with mean disease onset 10 years later than in carriers of two mutations but worse disease progression. A meta-analysis indicated that, in PINK1 heterozygotes, the PD risk is only slightly increased with a non significant odds ratio of 1.62. These findings suggest that PINK1 heterozygous rare variants play only a minor susceptibility role in the context of a multifactorial model of PD. Hence, their significance should be kept distinct from that of homozygous/compound heterozygous mutations, that cause parkinsonism inherited in a mendelian fashion.
Human Mutation 05/2008; 29(4):565. · 5.69 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Homozygous or compound heterozygous mutations in the PINK1 gene represent the second most frequent cause of autosomal recessive parkinsonism after Parkin. The phenotype differs from idiopathic Parkinson's disease for earlier onset, slower disease progression, and better response to therapy. Indeed, the rare patients with onset above 50 years are usually relatives of early-onset probands. Here, we report the first occurrence of compound heterozygous PINK1 mutations in a sporadic patient with a phenotype indistinguishable from idiopathic Parkinson's disease (PD), with onset in the late seventh decade, rapid progression and good response to levodopa that waned with time. Both mutations (p.A244G and p.V317I) were found to abolish the protective effect of wild-type PINK1 against staurosporine-induced apoptosis. These findings further expand the clinical spectrum of PINK1-related parkinsonism to include late onset, typical PD, and underline the existing difficulties in discriminating between mendelian parkinsonism and idiopathic PD.
Movement Disorders 05/2008; 23(6):881-5. · 4.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Growing interest is present in literature on the study of prospective memory functioning in Parkinson's disease (PD). Current data indicate that prospective memory may be impaired in PD and a relationship with general executive dysfunctioning has been suggested. However, although the dopamine dependency of cognitive dysfunction in PD has been widely investigated, poor is known on the dopaminergic modulation of PM. In the present study we explored the effect of acute administration of levodopa on the performance of a PD sample (n=20) in a time-based prospective memory task. PD patients were evaluated in the morning after a 12-hour therapy wash-out in two experimental conditions: i) after levodopa assumption ("on"); ii) without drug administration ("off"). The experimental task required to execute three uncorrelated actions after 10' for three consecutive trials. Distinct scores for the spontaneous recall of the intention to perform the actions (prospective component) and for the correct execution of the actions (retrospective component) have been computed. Results showed that in the "off" condition PD patients were selectively impaired on the prospective component of the task. However, L-dopa administration significantly improved PD patients' performance actually restoring the prospective memory deficit. These results support a critical role of dopaminergic modulation in prospective memory processes in PD patients, possibly through the replacement of dopamine levels in fronto-striatal pathways.
Behavioural neurology 02/2008; 19(1-2):45-8. · 1.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Gait disturbances and akinesia are extremely disabling in advanced Parkinson's disease. It has been suggested that modulation of the activity of the pedunculopontine nucleus (PPN) may be beneficial in the treatment of these symptoms. We report the clinical affects of deep brain stimulation (DBS) in the PPN and subthalamic nucleus (STN). Six patients with unsatisfactory pharmacological control of axial signs such as gait and postural stability underwent bilateral implantation of DBS electrodes in the STN and PPN. Clinical effects were evaluated 2-6 months after surgery in the OFF- and ON-medication state, with both STN and PPN stimulation ON or OFF, or with only one target being stimulated. Bilateral PPN-DBS at 25 Hz in OFF-medication produced an immediate 45% amelioration of the motor Unified Parkinson's Disease Rating Scale (UPDRS) subscale score, followed by a decline to give a final improvement of 32% in the score after 3-6 months. In contrast, bilateral STN-DBS at 130-185 Hz led to about 54% improvement. PPN-DBS was particularly effective on gait and postural items. In ON-medication state, the association of STN and PPN-DBS provided a significant further improvement when compared to the specific benefit mediated by the activation of either single target. Moreover, the combined DBS of both targets promoted a substantial amelioration in the performance of daily living activities. These findings indicate that, in patients with advanced Parkinson's disease, PPN-DBS associated with standard STN-DBS may be useful in improving gait and in optimizing the dopamine-mediated ON-state, particularly in those whose response to STN only DBS has deteriorated over time. This combination of targets may also prove useful in extra-pyramidal disorders, such as progressive supranuclear palsy, for which treatments are currently elusive.
Brain 07/2007; 130(Pt 6):1596-607. · 9.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine whether low-frequency repetitive transcranial magnetic stimulation (rTMS) may modulate l-DOPA-induced dyskinesia (LID) in dyskinetic Parkinson's disease (PD) patients. LID is a severe motor complication in advanced PD patients. The neural mechanisms involved in LID are not clear, and it is apparent that both an excessive decrease in internal pallidus firing and a modification and overactivation of cortical motor and premotor areas are involved in its pathogenesis.
Using low frequency 1Hz repetitive rTMS we investigated whether decrease of excitability of the supplementary motor area (SMA) may result in modification of LID in PD patients. Furthermore we tested whether it was possible to enhance and/or prolong the beneficial effects of the treatment with repeated sessions of stimulation.
We observed that 1Hz rTMS induced a transient reduction of dyskinesias. A single session of rTMS improved LID, while repeated sessions of stimulation failed to enhance and/or prolong the beneficial effects of the procedure, without causing motor deterioration or other adverse effects.
These results suggest that LID may depend on an increased excitability of the SMA.
SMA rTMS is effective in reducing transiently LID, although cannot yet be considered clinically useful.
Clinical Neurophysiology 10/2006; 117(9):1917-21. · 3.41 Impact Factor
-
Roberta Marongiu,
Daniele Ghezzi,
Tamara Ialongo,
Francesco Soleti,
Antonio Elia,
Stefania Cavone,
Alberto Albanese,
Maria Concetta Altavista,
Paolo Barone, Livia Brusa,
Pietro Cortelli,
Lucia Petrozzi,
Cesa Scaglione,
Paolo Stanzione,
Michele Tinazzi,
Massimo Zeviani,
Bruno Dallapiccola,
Anna Rita Bentivoglio,
Enza Maria Valente,
Barbara Garavaglia
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the frequency of the LRRK2 G2019S mutation in Italy, we tested 1,072 probands with Parkinson's disease (PD; 822 sporadic and 250 familial): 20 patients (1.9%) carried the G2019S mutation, 11 patients (1.3%) were sporadic, and 9 (4.3%) had a positive family history. Considering only probands with autosomal dominant inheritance, the G2019S frequency raises to 5.2%. All presented a typical phenotype with variable onset and shared the common ancestral haplotype. Mutation frequency raised from 1.2% in early onset PD to 4.0% in late onset PD.
Movement Disorders 09/2006; 21(8):1232-5. · 4.51 Impact Factor
-
Salvatore Galati,
Paolo Mazzone,
Ernesto Fedele,
Antonio Pisani,
Antonella Peppe,
Mariangela Pierantozzi, Livia Brusa,
Domenicantonio Tropepi,
Vincenzo Moschella,
Maurizio Raiteri,
Paolo Stanzione,
Giorgio Bernardi,
Alessandro Stefani
[show abstract]
[hide abstract]
ABSTRACT: To understand the events underlying the clinical efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN), electrophysiological recordings and microdialysis evaluations were carried out in the substantia nigra pars reticulata (SNr), one of the two basal ganglia (BG) nuclei targeted by STN output, in patients with Parkinson's disease (PD). Clinically effective STN-DBS caused a significant increase of the SNr firing rate. The poststimulus histogram (PSTH) showed an excitation peak at 1.92-3.85 ms after the STN stimulus. The spontaneous discharge of SNr neurons was driven at the frequency of the stimulation (130 Hz), as shown in the autocorrelograms (AutoCrl). The fast Fourier transform (FFT) analysis showed a peak at 130 Hz, and a less pronounced second one at 260 Hz. Accordingly, in the distribution of the interspike intervals (ISIs), the mode was earlier, and skewness more asymmetric. Biochemically, the increased excitatory driving from the STN was reflected by a clear-cut increase in cyclic guanosine 3',5'-monophosphate (cGMP) levels in the SNr. These results indicate that the beneficial effect of DBS in PD patients is paralleled with a stimulus-synchronized activation of the STN target, SNr. Our findings suggest that, during STN-DBS, a critical change towards a high-frequency oscillatory discharge occurs.
European Journal of Neuroscience 07/2006; 23(11):2923-8. · 3.63 Impact Factor
