Daniela Frosini

Università di Pisa, Pisa, Tuscany, Italy

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Publications (48)191.35 Total impact

  • Movement Disorders 06/2015; 30(8). DOI:10.1002/mds.26255 · 5.68 Impact Factor
  • S Mazzucchi · D Frosini · U Bonuccelli · R Ceravolo ·
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    ABSTRACT: Levodopa-induced dyskinesias (LID) are one of the main issues in the management of Parkinson's disease (PD); once these dyskinesias are established treatment becomes difficult, so preventive strategies should be first evaluated. Although levodopa (LD) treatment has recently been related as risk factor for LID, the main strategy to delay LID is to start PD treatment with dopamine agonists, adding LD at low doses. After LID onset, approaches include reducing single LD doses, reducing or discontinuing monoamine oxidase type B/catechol O-methyltransferase (MAO-B/COMT) inhibitors and extended-release (ER) LD. Amantadine represents the best antidyskinetic tool, and ER amantadine is the most promising upcoming antidyskinetic drug. New LD formulations such as IPX-066 (able to provide continuous dopaminergic stimulation) also represent promising new approaches. The involvement of a nondopaminergic system in the pathogenesis of LID suggests that the modulation of glutamate, serotonin and adenosine could have potential as new upcoming drug targets, but the role of such drugs will still need to be confirmed in randomized controlled trials. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.
    Drugs of today (Barcelona, Spain: 1998) 05/2015; 51(5):315-329. DOI:10.1358/dot.2015.51.5.2313726 · 1.20 Impact Factor
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    ABSTRACT: We investigated the striatal and extrastriatal DAT availability (SPM8) by [(123)I]FP-CIT-SPECT in 15 PD patients with depression and 35 PD patients without depression. A cluster with significant (p < 0.05) lower tracer binding in PD with depression was found in left cingulate cortex, persistent after correction for age, disease severity and duration, and inversely correlated with depression scores (r -0.336, p < 0.05). Our data indicate a significant association between PD depression and cingulate dopaminergic denervation supporting the dopaminergic hypothesis of PD depression.
    Journal of Neural Transmission 01/2015; 333(8). DOI:10.1007/s00702-015-1370-z · 2.40 Impact Factor
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    ABSTRACT: The etiopathogenesis of essential tremor (ET) is still debated, since the predominant role of circuit dysfunction or brain degenerative changes has not been clearly established. The relationship with Parkinson’s Disease (PD) is also controversial and resting tremor occurs in up to 20 % of ET. We investigated the morphological and functional changes associated with ET and we assessed potential differences related to the presence (ET+R) or absence (ET−R) of resting tremor. 32 ET patients (18 ET+R; 14 ET−R) and 12 healthy controls (HC) underwent 3T-MRI protocol including Spoiled Gradient T1-weighted sequence for Voxel-Based Morphometry (VBM) analysis and functional MRI during continuous writing of “8” with right dominant hand. VBM analysis revealed no gray and white matter atrophy comparing ET patients to HC and ET+R to ET−R patients. HC showed a higher BOLD response with respect to ET patients in cerebellum and other brain areas pertaining to cerebello-thalamo-cortical circuit. Between-group activation maps showed higher activation in precentral gyrus bilaterally, right superior and inferior frontal gyri, left postcentral gyrus, superior and inferior parietal gyri, mid temporal and supramarginal gyri, cerebellum and internal globus pallidus in ET−R compared to ET+R patients. Our findings support that the dysfunction of cerebello-thalamo-cortical network is associated with ET in absence of any morphometric changes. The dysfunction of GPi in ET+R patients, consistently with data reported in PD resting tremor, might suggest a potential role of this structure in this type of tremor.
    Journal of Neurology 01/2015; 262(3). DOI:10.1007/s00415-014-7626-y · 3.38 Impact Factor
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    ABSTRACT: Background and purpose: Standard neuroimaging fails in defining the anatomy of the substantia nigra and has a marginal role in the diagnosis of Parkinson disease. Recently 7T MR target imaging of the substantia nigra has been useful in diagnosing Parkinson disease. We performed a comparative study to evaluate whether susceptibility-weighted angiography can diagnose Parkinson disease with a 3T scanner. Materials and methods: Fourteen patients with Parkinson disease and 13 healthy subjects underwent MR imaging examination at 3T and 7T by using susceptibility-weighted angiography. Two expert blinded observers and 1 neuroradiology fellow evaluated the 3T and 7T images of the sample to identify substantia nigra abnormalities indicative of Parkinson disease. Diagnostic accuracy and intra- and interobserver agreement were calculated separately for 3T and 7T acquisitions. Results: Susceptibility-weighted angiography 7T MR imaging can diagnose Parkinson disease with a mean sensitivity of 93%, specificity of 100%, and diagnostic accuracy of 96%. 3T MR imaging diagnosed Parkinson disease with a mean sensitivity of 79%, specificity of 94%, and diagnostic accuracy of 86%. Intraobserver and interobserver agreement was excellent at 7T. At 3T, intraobserver agreement was excellent for experts, and interobserver agreement ranged between good and excellent. The less expert reader obtained a diagnostic accuracy of 89% at 3T. Conclusions: Susceptibility-weighted angiography images obtained at 3T and 7T differentiate controls from patients with Parkinson disease with a higher diagnostic accuracy at 7T. The capability of 3T in diagnosing Parkinson disease might encourage its use in clinical practice. The use of the more accurate 7T should be supported by a dedicated cost-effectiveness study.
    American Journal of Neuroradiology 11/2014; 36(3). DOI:10.3174/ajnr.A4158 · 3.59 Impact Factor
  • Article: Response.

    Radiology 11/2014; 273(2):628-9. · 6.87 Impact Factor
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    ABSTRACT: Background Serotonergic system is believed to play a role in levodopa-induced-dyskinesias pathogenesis, and serotonin transporter has been evaluated as potential target.Aim of the studyTo retrospectively investigate the potential effect of selective serotonin reuptake inhibitors (SSRIs) during dopaminergic treatment, in the development of dyskinesias in patients with Parkinson's disease (PD).Methods One hundred and thirty-five consecutive patients with PD, with 10-year follow-up since diagnosis. Age at PD onset, duration of levodopa treatment, maximum daily dose, and SSRIs exposure were collected. Risk, latency, and severity of dyskinesias were evaluated comparing patients with and without SSRIs exposure.ResultsForty-nine patients received SSRIs for a variable period, 86 were never treated; no significant difference between the groups was observed (P = 0.897) in the prevalence of dyskinesias. Considering latency between PD diagnosis and dyskinesias onset, patients exposed to SSRIs developed dyskinesias later (6.48 ± 1.99 vs 5.70 ± 1.89 years, P = 0.020). The median dyskinesia severity score was 0 in the exposed group vs 1 in non-exposed patients (P = 0.025). Multivariate analysis demonstrated SSRIs exposure as the only independent predictor, protecting from severe dyskinesia.Conclusions Use of SSRIs in patients with PD did not protect from dyskinesias; however, exposure may delay the onset and reduce the severity, confirming modulation of the serotonergic system as possible antidyskinetic strategy.
    Acta Neurologica Scandinavica 09/2014; 131(3). DOI:10.1111/ane.12314 · 2.40 Impact Factor
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    ABSTRACT: An overactive striatal dopaminergic neurotransmission is described in psychosis and may be associated with a state of aberrant salience attribution. This pilot psychometric study investigated if features suggestive of an aberrant salience state, a condition of psychosis proneness, are associated with dopamine replacement therapy in patients with early Parkinson's disease (PD). 77 participants (50 medicated PD patients, 12 newly diagnosed drug-naive PD patients and 15 healthy controls) were enrolled and assessed with the Aberrant Salience Inventory (ASI). Differences between groups were found for ASI scores, and ASI scores correlated with the dopaminergic therapy, in particular levodopa. These findings preliminary suggested that the presence and the degree of an aberrant salience state may be associated with features of the dopaminergic therapy; further studies are needed to investigate which neuropsychiatric complications more common in PD patients may be characterized by an underlying aberrant salience state.
    Neurological Sciences 07/2014; 35(10). DOI:10.1007/s10072-014-1874-6 · 1.45 Impact Factor
  • M Cosottini · D Frosini · L Biagi · I Pesaresi · M Costagli · G Tiberi · M Symms · M Tosetti ·
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    ABSTRACT: To study patient tolerability of brain imaging that employs an ultrahigh field (7 T) MR system METHODS: We examined 180 subjects that underwent brain MR examination at 7 T. A tolerability test consisting of two parts (during patient table motion and during the examination) was administered to all subjects in order to monitor their discomfort. The scores range from 0 to 5 for the first part, and from 0 to 10 for the second part, the total score of each subject therefore ranging from 0 (no side effects reported) to 15 (lowest tolerability) RESULTS: A total of 51 % of subjects reported at least one side effect but all were mild in intensity and did not require examination interruption. No serious adverse event was reported. The total score (mean ± standard deviation) was 1.1 ± 1.5 out of 15 (mean score 0.4 ± 0.7 out of 5 during patient table motion and 0.7 ± 1.1 out of 10 during MR). Patient discomfort was not related to gender or health status, but it was reduced with time after system installation with increasing operator experience in performing UHF MR examinations. Ultrahigh field MRI is well tolerated without excessive discomfort to subjects. • 7-T MRI is well tolerated with low incidence of side effects • The subjects' discomfort during 7-T MRI is reduced as the operators' experience increases • 7-T MRI is practicable in healthy subjects and patients with neurodegenerative diseases.
    European Radiology 05/2014; 24(8). DOI:10.1007/s00330-014-3177-y · 4.01 Impact Factor

  • Joint Congress of European Neurology; 05/2014
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    ABSTRACT: Purpose: To evaluate the anatomy of the substantia nigra (SN) in healthy subjects by performing 7-T magnetic resonance (MR) imaging of the SN, and to prospectively define the accuracy of 7-T MR imaging in distinguishing Parkinson disease (PD) patients from healthy subjects on an individual basis. Materials and methods: The 7-T MR imaging protocol was approved by the Italian Ministry of Health and by the local competent ethics committee. SN anatomy was described ex vivo on a gross brain specimen by using highly resolved proton-density (spin-echo proton density) and gradient-recalled-echo (GRE) images, and in vivo in eight healthy subjects (mean age, 40.1 years) by using GRE three-dimensional multiecho susceptibility-weighted images. After training on appearance of SN in eight healthy subjects, the SN anatomy was evaluated twice by two blinded observers in 13 healthy subjects (mean age, 54.7 years) and in 17 PD patients (mean age, 56.9 years). Deviations from normal SN appearance were described and indicated as abnormal, and both diagnostic accuracy and intra- and interobserver agreement for diagnosis of PD with 7-T MR imaging were calculated. Results: Three-dimensional multiecho susceptibility-weighted 7-T MR imaging reveals a three-layered organization of the SN allowing readers to distinguish pars compacta ventralis and dorsalis from pars reticulata. The abnormal architecture of the SN allowed a discrimination between PD patients and healthy subjects with sensitivity and specificity of 100% and 96.2% (range, 92.3%-100%), respectively. Intraobserver agreement (κ = 1) and interobserver agreement (κ = 0.932) were excellent. Conclusion: MR imaging at 7-T allows a precise characterization of the SN and visualization of its inner organization. Three-dimensional multiecho susceptibility-weighted images can be used to accurately differentiate healthy subjects from PD patients, which provides a novel diagnostic opportunity.
    Radiology 02/2014; 271(3):131448. DOI:10.1148/radiol.14131448 · 6.87 Impact Factor

  • Neurological Sciences 02/2014; 35(6). DOI:10.1007/s10072-014-1672-1 · 1.45 Impact Factor
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    ABSTRACT: Similarly to subjects with degenerative parkinsonism, (123)I-FP-CIT SPECT has been reported either normal or abnormal in patients with drug-induced parkinsonism (DIP), challenging the notion that parkinsonism might be entirely due to post-synaptic D2-receptors blockade by antipsychotic drugs. In a previous multicenter cross-sectional study conducted on a large sample of patients with schizophrenia, we identified 97 patients who developed parkinsonism with a similar bi-modal distribution of DAT-SPECT. In this longitudinal study, we reported clinical and imaging features associated with progression of motor disability over 2-year follow-up in 60 out of those 97 patients with schizophrenia and parkinsonism who underwent (123)I-FP-CIT SPECT at baseline evaluation (normal SPECT=33; abnormal SPECT=27). As second end-point, chronic response to levodopa over a 3-month period was tested in a subgroup of subjects. Motor Unified Parkinson's Disease Rating Scale (UPDRS) at follow-up significantly increased in patients with abnormal SPECT. Specifically, a 6-point worsening was demonstrated in 18.5% of the subjects with abnormal SPECT and in none of the subjects with normal SPECT. Levodopa treatment improved motor UPDRS only in the group with abnormal SPECT. After adjustment for possible confounders, linear regression analysis demonstrated that abnormal SPECT findings at baseline were the only predictor of motor disability progression and of better outcome of levodopa treatment. Our results support the notion that a degenerative disease might underlie parkinsonism in a minority of schizophrenic patients chronically exposed to antipsychotics. Functional imaging of the dopamine transporter can be helpful to select this patient sub-group that might benefit from levodopa therapy.
    Schizophrenia Research 12/2013; 152(2-3). DOI:10.1016/j.schres.2013.11.028 · 3.92 Impact Factor
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    ABSTRACT: The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson's disease (PD) and to evaluate the role of levodopa exposure as a potential risk factor. A multicenter study of 330 patients with PD and 137 healthy controls with a comparable age distribution was performed. With respect to levodopa exposure, 144 patients had long exposure (≥3 years) to levodopa (LELD), 103 patients had short exposure (<3 years) to levodopa (SELD), and 83 patients had no exposure to levodopa (NOLD). Nerve function was evaluated using the reduced total neuropathy score. Right sural sensory antidromic and peroneal motor nerve conduction studies were performed by neurophysiologists who were blinded to the existence of neuropathy clinical features or PD treatment. Overall, 19.40% of patients in the LELD group, 6.80% in the SELD group, 4.82% in the NOLD group, and 8.76% in the control group were diagnosed with neuropathy (axonal, predominantly sensory). Multivariate logistic analysis indicated that the risk of neuropathy was not influenced by disease duration, severity, or sex. The risk of neuropathy increased by approximately 8% for each year of age (P < 0.001; odds ratio [OR], 1.08; 95% confidence interval [CI], 1.037-1.128). The risk of neuropathy was 2.38 higher in the LELD group than in the control group (P = 0.022; OR, 2.38; 95% CI, 1.130-5.014). In a comparison between patients with and without neuropathy (Student's t test), the levodopa dose was higher (P < 0.0001), serum vitamin B12 levels were lower (P = 0.0102), and homocysteine levels were higher (P < 0.001) in the patients with neuropathy. Our results demonstrate that the duration of exposure to levodopa, along with age, is the main risk factor for the development of neuropathy. Screening for homocysteine and vitamin B12 levels and clinical-neurophysiological monitoring for neuropathy may be advisable in patients with PD who are receiving treatment with levodopa. © 2013 Movement Disorder Society.
    Movement Disorders 09/2013; 28(10). DOI:10.1002/mds.25585 · 5.68 Impact Factor
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    ABSTRACT: OBJECTIVE To assess the association between clinical and socio-demographic features and anti-Parkinson drug (APD) treatment modifications in patients with PD and to describe neurologist and patient opinions regarding the need for changes in APD therapy. METHODS: Subjects with PD with stable APD treatment over ≥3 months prior to baseline were enrolled and evaluated for socio-demographic data, disability, disease severity and neurologist and patient views on the need to modify APD treatment. RESULTS: 775 Patients were included, 51% with Hoehn and Yahr (HY) stage 1-2 (early PD) and 49% with HY stage 2.5-4 (advanced PD). Neurologists modified APD treatment in 255 patients, 97 (25%) early PD and 158 (41%; p < 0.0001) advanced PD. APD modification was strongly associated with a low educational level and UPDRS part IV score. The most common reasons behind the APD therapy changes among neurologists were presence/worsening of motor or non-motor symptoms (88% and 37% of subjects respectively). Out of 216 patients, 92% and 51% were willing to undergo APD changes to therapy because of the presence/worsening of motor or non-motor symptoms. CONCLUSIONS: Neurologist decision to change APD therapy and patients reasons for dissatisfaction with it can be prevalently attributed to the presence/worsening of motor symptoms and motor fluctuations in the advanced stages. Non-motor symptoms were considered more often by patients. The patient educational level played a key role in treatment decision.
    Parkinsonism & Related Disorders 08/2013; DOI:10.1016/j.parkreldis.2013.08.006 · 3.97 Impact Factor
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    ABSTRACT: Information about patients' adherence to therapy represents a primary issue in Parkinson's disease (PD) management. To perform the linguistic validation of the Italian version of the self-rated 8-Item Morisky Medical Adherence Scale (MMAS-8) and to describe in a sample of Italian patients affected by PD the adherence to anti-Parkinson drug therapy and the association between adherence and some socio-demographic and clinical features. MMAS-8 was translated into Italian language by two independent Italian mother-tongue translators. The consensus version was then back-translated by an English mother-tongue translator. This translation process was followed by a consensus meeting between the authors of translation and investigators and then by two comprehension tests. The translated version of the MMAS-8 scale was then administered at the baseline visit of the "REASON" study (Italian Study on the Therapy Management in Parkinson's disease: Motor, Non-Motor, Adherence and Quality Of Life Factors) in a large sample of PD patients. The final version of the MMAS-8 was easily understood. Mean ± SD MMAS-8 score was 6.1 ± 1.2. There were no differences in adherence to therapy in relationship to disease severity, gender, educational level or decision to change therapy. The Italian version of MMAS-8, the key tool of the REASON study to assess the adherence to therapy, has shown to be understandable to patients with PD. Patients enrolled in the REASON study showed medium therapy adherence.
    Neurological Sciences 06/2013; DOI:10.1007/s10072-013-1438-1 · 1.45 Impact Factor
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    ABSTRACT: The side of motor symptom predominance may influence cognitive performance in patients with Parkinson's disease (PD): PD patients with right-side motor symptom predominance typically present difficulties in tasks of language and verbal memory, whereas PD patients with left-side motor symptom predominance typically present difficulties in visuospatial tasks. The current study aimed at investigating the relationship between motor symptom lateralization and cognitive performance in PD patients without the possible confounding effect of dopaminergic drugs, which may enhance or impair cognition on the basis of assessed function and disease stage. From the initial sample of 137 consecutive newly diagnosed drug-naïve (de novo) PD patients, clinical follow-ups and neurological examinations identified 108 right-handed patients with a unilateral motor presentation or a clear motor asymmetry (59 right-PD: 54.6%; 49 left-PD: 45.4%). Any cognitive difference emerged between right-PD patients and left-PD patients at this disease stage. Scores of lateralized motor impairment severity correlated with some cognitive performances: Right motor impairment correlated with a measure of set shifting (Trail Making Test B-A), and left motor impairment correlated with phonemic fluency and tasks with visuospatial material (Colored Progressive Matrices of Raven, Rey-Osterrieth Complex Figure Copy and Immediate Recall). Findings of the current study supported the conclusion that the side of clinical motor predominance scarcely influences cognition in the early untreated stages of PD, suggesting that cognitive differences between subgroups of lateralized PD patients probably may appear in more advanced disease stages.
    Journal of Clinical and Experimental Neuropsychology 12/2012; 35(2). DOI:10.1080/13803395.2012.751966 · 2.08 Impact Factor
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    Schizophrenia Research 12/2012; 142(s 1–3):251. DOI:10.1016/j.schres.2012.08.009 · 3.92 Impact Factor
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    Michele Poletti · Daniela Frosini · Roberto Ceravolo · Ubaldo Bonuccelli ·

    Movement Disorders 11/2012; 27(13):1706. DOI:10.1002/mds.25120 · 5.68 Impact Factor
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    ABSTRACT: The investigation of the relationship between affective symptoms and dopamine transporter (DAT) density provided conflicting data in both Parkinson's disease (PD) and non-PD patients. However, the potential interference of psychoactive as well as anti-parkinsonian drugs on DAT density should be taken into account. To investigate the relationship between affective symptoms and pre-synaptic dopaminergic function in de novo PD patients. Forty-four de novo PD consecutive outpatients were recruited, and the severity of anxious symptoms was evaluated with the Hamilton Anxiety Rating Scale (HAM-A), the severity of depressive symptoms with the Hamilton Depression Scale (HAM-D) and the Beck Depression Inventory (BDI). Six patients had a formal diagnosis of depression. All patients performed 123I-FP-CIT SPECT, and semi-quantitative striatal indices were calculated. Disease severity, as measured by Unified Parkinson's Disease Rating Scale (UPDRSIII), was inversely correlated with bilateral striatal indices. Bilateral striatal uptake was significantly positively correlated with HAM-D (r.329; r.423, respectively, right and left), BDI (r.377; r.360, respectively, right and left) and HAM-A (r.338; r.340, respectively, right and left). After controlling for age, disease duration and severity, and Mini Mental State Examination (MMSE), no significant reduction in r-values was observed (P < 0.05). Our data support the existence of a relationship between depressive and anxious symptoms and the striatal 123I-FP-CIT uptake. The finding of an increased DAT density associated with mild affective symptoms could be due to the lack of compensatory mechanisms usually present in early PD, and/or it might have a pathogenic role in affective symptoms by reducing the dopaminergic tone in the synaptic cleft.
    European Journal of Neurology 10/2012; 20(3). DOI:10.1111/j.1468-1331.2012.03878.x · 4.06 Impact Factor

Publication Stats

511 Citations
191.35 Total Impact Points


  • 1970-2015
    • Università di Pisa
      • Department of Clinical and Experimental Medicine
      Pisa, Tuscany, Italy
  • 2014
    • Santa Chiara Hospital
      Trient, Trentino-Alto Adige, Italy