[Show abstract][Hide abstract] ABSTRACT: The study analyzes the presence of dyskinesias-reduced-self-awareness in forty-eight patients suffering from Parkinson’s disease (PD). As the association with executive dysfunction is a matter of debate and we hypothesize it plays an important role in dyskinesias self-unawareness, we analyzed the role of dopaminergic treatment on the medial-prefrontal-ventral-striatal circuitry using a neurocognitive approach. Special attention was given to metacognitive abilities related to action-monitoring that represent a novel explanation of the phenomenon.
PD patients were assessed using different rating scales that we devised to measure movement awareness disorders. In order to ascertain whether each variable measured at a cognitive-clinical level contributes to predicting the scores of the movement-disorder-awareness-scales, we conducted multiple logistic regression models using the latter as binary dependent variables. We used the Wisconsin Card Sorting Test-metacognitive-version to assess the executive functions of the prefrontal-ventral-striatal circuitry.
Data showed that a reduction of self-awareness using the Dyskinesia rating scale was associated with global monitoring (p=.04), monitoring resolution (p=.04) and control sensitivity (p=.04). Patients failed to perceive their performance, distinguish between correct and incorrect sorts, be confident in their choice and consequently decide to gamble during the task.
We did not find any association with executive functions using the Hypo-Bradykinesia rating scale.
Our findings indicate that when the comparator mechanism for monitoring attentive performance is compromised at a prefrontal striatal level, patients lose the ability to recognize their motor disturbances that do not achieve conscious awareness.
Key words: awareness of movement disorders, dyskinesias, Parkinson’s disease, self-awareness, metacognitive functions
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) on alexithymia, a deficit in affective regulation, comparing patients with Parkinson's disease (PD) submitted to STN-DBS (DBS group) to PD patients not yet treated with STN-DBS (pre-DBS group) and to healthy participants (C group).
Frontiers in Psychology 10/2014; 5(1168). · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This multi-center Italian prospective observational study reports the 4 months follow-up data of 87 patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) shifted from intravenous to subcutaneous immunoglobulin treatment. A therapeutic shift from intravenous to subcutaneous immunoglobulin was performed in 87 patients (66 CIDP; 21 MMN) affected by immune-mediated peripheral neuropathies with evidence of a sustained clinical response to intravenous immunoglobulin. Patients were evaluated by means of the Overall Neuropathy Limitation Scale, Medical Research Council Scale and Life Quality Index questionnaire, both at the time of therapeutic shift and after 4 months of subcutaneous immunoglobulin treatment. A sustained clinical efficacy was observed after the switch to subcutaneous immunoglobulin: the Overall Neuropathy Limitation Scale score improved in the group of 66 CIDP patients (P = 0.018), with only one subject reporting a worsening of 1 point, and remained stable in the group of 21 MMN patients (P = 0.841), with one subject reporting a worsening of two points. An improvement in the patient's perception of therapeutic setting was reported in both groups. This large multi-center study confirms the short-term clinical equivalence of subcutaneous versus intravenous immunoglobulin and a possible improvement in the patient's perception of therapeutic setting with the subcutaneous administration. However, further studies are required to extend the results to a longer observational period.
Journal of Neurology 08/2014; · 3.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the frequency of symptoms of impulse control disorders (ICD, namely pathological gambling, compulsive sexual behaviour, compulsive eating and compulsive shopping) and related behaviours (hobbyism, punding, walkabout and dopamine dysregulation syndrome) in patients with Parkinson's disease (PD) with and without probable rapid eye movement, sleep behaviour disorder (pRBD).
Journal of neurology, neurosurgery, and psychiatry. 07/2014;
[Show abstract][Hide abstract] ABSTRACT: This observational study reports the long-term follow-up of 184 Parkinson's disease (PD) patients treated with subthalamic deep brain stimulation (STN-DBS), retrospectively analyzing the outcomes of subjects with pre-surgical mild cognitive impairment (MCI) compared to those of patients with normal cognition. Patients were divided into PD-MCI or normal cognition groups at baseline, and then compared after 1, 3, 5 and >5 years of follow-up. Subjects assessed by outpatient clinical follow-up evaluation, not performing a complete clinical and neuropsychological follow-up assessment, were separately considered and rated according to their functional autonomy in daily living activities. The MCI prevalence at baseline was 23 %, increasing to 34 % at 1 year and over 40 % after 3 years. Dementia progressively affected more than 30 % of subjects after a median time of 6 years in the PD-MCI group and 11 years in the normal cognition group (p: 0.028). The mortality risk was slightly higher in PD-MCI patients. Outpatient clinical evaluations showed a progressive increase of subjects completely dependent in the activities of daily living, which ranged from the 11 % at 3 years to 23 % at 5 years and 31 % at >5 years. MCI can be frequently observed in PD patients, possibly influencing the outcome of surgical therapy. Our findings confirm the sustained long-lasting efficacy of STN-DBS on motor functions in both PD-MCI and normal cognition subjects. PD-MCI patients showed a more precocious cognitive impairment, as expected by natural history studies, but no case of dementia was observed early after surgery.
Journal of Neurology 06/2014; · 3.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diagnosis of Parkinson's disease, the second most common neurodegenerative disease, is based on the appearance of motor symptoms. A panel of protein biomarkers in the T-lymphocyte proteome was previously proposed as a Parkinson's disease signature. Here, we designed an LC-MS based method to quantitatively evaluate this protein signature by multiple reaction monitoring (MRM) in T-lymphocytes and peripheral blood mononuclear cells from a new cohort of nine patients with Parkinson's disease and nine unaffected subjects. Patients were classified using the discriminant function obtained from two-dimensional electrophoresis and protein amounts measured by MRM, thus assigning seven controls out of nine as true negatives and nine patients out of nine as true positives. A good discriminant power was obtained by selecting a subset of peptides from the protein signature, with an area under the receiver operating characteristic curve of 0.877. A similar result is achieved by evaluating all peptides of a selected panel of proteins (Gelsolin, Moesin, Septin-6, Twinfilin-2, Lymphocyte-specific protein 1, Vimentin, Transaldolase), with an area under curve of 0.840. Conversely, the signature was not able to classify the enrolled subjects when evaluated in whole mononuclear cells. Overall, this report shows the portability of the proposed method to a large-scale clinical validation study.
Journal of Proteome Research 06/2014; · 5.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) is an effective treatment for Parkinson’s disease (PD), but only few studies investigated its long-term efficacy. Furthermore, little is known about the role of PD-subtype on STN-DBS long-term outcome.
To report the results of a long-term follow-up (mean 11 years, range 10-13) on 26 patients bilaterally implanted in two centres.
Patients were assessed preoperatively and 1, 5 and 11 years after the implant by the Unified Parkinson’s Disease Rating Scale (UPDRS) and a battery of neuropsychological tests. Stimulation parameters, drugs dosages, non-motor symptoms and adverse events were also recorded.
At 11 years, stimulation significantly improved the motor symptoms by 35.8%, as compared to the preoperative off-state. Motor complications were well controlled, with a 84.6% improvement of dyskinesias and a 65.8% improvement of motor fluctuations. Despite this, the UPDRS-II-on score worsened by 88.5%, mainly for the worsening of poorly levodopa-responsive symptoms. More than 70% of the patients performed in the normal range in most of the neuropsychological tests, despite the development of dementia in 22.7%. Age at disease onset, axial subscore in off-condition and presence of REM behaviour disorder at baseline were found to be associated with a higher risk of developing disability over time.
Our study confirms the long-term safety and efficacy of STN-DBS in PD. Nevertheless, the functionality of patients worsens over time, mainly for the onset and progression of levodopa-resistant and non-motor symptoms. The role of PD-subtype seems to be relevant in the long-term outcome.
Parkinsonism & Related Disorders 04/2014; · 4.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
Assessing the frequency of Wearing-Off (WO) in Parkinson's disease (PD) patients, and its impact on Quality of Life (QoL).
Consecutive ambulatory patients, who were on dopaminergic treatment for ≥1 year, were included in this multicentre, observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as using the validated Italian version of a patient self-rated 19-question Wearing-Off Questionnaire (WOQ-19); WO was defined for scores ≥ 2. QoL was evaluated by the 8-item Parkinson's Disease Questionnaire (PDQ-8).
617 subjects were included, with a mean anti-Parkinson treatment duration of 6.6 ± 4.6 years, 87.2% were on levodopa treatment. Neurologists identified presence of WO in 351 subjects (56.9%), whereas 415 subjects (67.3%) were identified by the self-administered WOQ-19. In patients with a <2.5 years disease duration, WO was diagnosed in 12 subjects (21.8%) by neurologists and in 23 subjects (41.8%) by the WOQ-19. The most frequent WO symptoms, as identified by WOQ-19, were “slowness of movements” (55.8%) and “reduced dexterity” (48.8%). Younger age, female gender, Unified Parkinson's Disease Rating Scale (UPDRS) part II score and duration of anti-Parkinson treatment were found significantly associated with WO. The number of motor (p < 0.0001) and non-motor (p < 0.0001) WO symptoms correlated with PDQ-8 total score.
WO is common already at the early stages of PD and is underestimated by routine neurological clinical evaluation. The number of WO symptoms, both motor and non motor, increases along with disease duration and has a negative impact on patients QoL.
Parkinsonism & Related Disorders 02/2014; 20(2):204–211. · 4.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prior researches have suggested that home-based subcutaneous immunoglobulin (SCIG) is equally effective and can be less expensive than hospital-based intravenous immunoglobulin (IVIG) in treating chronic inflammatory demyelinating polyneuropathy (CIDP) patients. This economic evaluation aims at comparing costs of SCIG vs IVIG for CIDP patients in Italy. A 1-year model-based cost-minimization analysis basically populated via neurologists' opinion was undertaken from a societal perspective. Health care resources included immunoglobulin; drugs for premedication and complications (rash, headache, and hypertension) management; time of various health care professionals; pump for SCIG self-administration; infusion disposables. Non-health care resources encompassed transport and parking; losses of working and leisure time for patients and caregivers. Unit or yearly costs for resources valuation were mainly obtained from published sources. Costs were expressed in Euro ( ) 2013. An extensive one-way sensitivity analysis (OWSA) and a scenario SA tested the robustness of the base case findings. Overall costs per patient amount to 49,534.75 (SCIG) and 50,895.73 (IVIG); saving in favour of SCIG reaches 1360.98. For both SCIG and IVIG, the cost driver was immunoglobulin (94.06 vs 86.06 % of the overall costs, respectively). Sensitivity analyses confirmed the consistency of the baseline results. SCIG may be a cost-saving therapy for Italian CIDP patients.
[Show abstract][Hide abstract] ABSTRACT: Introduction. This study evaluates the efficacy of palmitoylethanolamide ultramicronized (PEA-um) as an add-on treatment in patients with diabetic or traumatic neuropathic pain (NP). Methods. 30 patients with chronic NP were assessed with Visual Analogue Scale (VAS), NP Symptom Inventory (NPSI), and Health Questionnaire Five Dimensions (EQ-5D), both at baseline and after 10 and 40 days of treatment with 1200 mg/die of PEA-um. All other therapies were maintained stable during the follow-up period. Results. VAS mean score significantly improved within the first 10 days, ranging from 8.20 ± 1.53 to 6.40 ± 1.83 (P < 0.002), with a further decrease to 5.80 ± 2.04 (P < 0.001) after 40 days of PEA-um administration. Moreover, NPSI total score improved from 5.2 ± 1.5 to 3.8 ± 2.1 (P: 0.025) and EQ-5D ranged from -0.30 ± 0.65 to 0.5 ± 0.34 (P < 0.001) between T0 and T2. Conclusions. This study reports the prospective short-term efficacy data of oral PEA-um in patients with diabetic or traumatic NP. A significant improvement was observed both in VAS and NPSI scores and in quality of life scales after 40 days of treatment, although some limitations should be considered, including the short followup and the open-label study design.
Pain research and treatment. 01/2014; 2014:854560.
[Show abstract][Hide abstract] ABSTRACT: Levodopa/carbidopa intestinal gel (LCIG) infusion is nowadays becoming an established therapeutic option for advanced Parkinson's disease (PD) patients with fluctuating symptoms unresponsive to conventional oral treatment. As the implementation of LCIG therapy is increasing, there is a need for safety and efficacy data from current clinical practice.
All PD patients treated with LCIG at our centre over a 7-year period were analysed to determine the duration of treatment, retention rate, reasons for discontinuation, LCIG efficacy in motor complications, modifications of concomitant therapy and adverse events.
Of the 59 patients, seven subjects (12%) died of causes unrelated to LCIG infusion and 11 patients (19%) discontinued therapy prior to the cut-off date. Duodopa improved motor complications and over 90% of patients reported an improvement in their quality of life, autonomy and clinical global status. The most common adverse events were dislocation and kinking of the intestinal tube.
LCIG infusion is effective for the long-term treatment of advanced PD patients and exerts a positive and clinically significant effect on motor complications with a relatively low dropout rate.
European Journal of Neurology 12/2013; · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Few clinical trials reported the comparative short-term efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) versus medical therapy in advanced Parkinson's disease (PD). However, the comparative efficacy, safety and the potential disease-modifying effect of these treatments have not been investigated over a longer follow-up period.
In this study, we organised a 'retrospective control group' to compare medical and surgical therapies over a long-term period. We assessed a group of PD patients suitable for STN-DBS but successively treated with medical therapies for reasons not related to PD, and a group of similar consecutive STN-DBS patients. We thus obtained two groups comparable at baseline, which were re-evaluated after an average follow-up of 6 years (range 4-11).
Patients treated with STN-DBS showed a long-lasting superior clinical efficacy on motor fluctuations, with a significant reduction in the average percentage of the waking day spent in 'OFF' and in the duration and disability of dyskinesia. Moreover, operated patients showed a better outcome in the activities of daily living in 'Medication-OFF' condition. On the other hand, a similar progression of motor score and cognitive/behavioural alterations was observed between the two groups, apart from phonemic verbal fluency, which significantly worsened in STN-DBS patients.
To our knowledge, this is the first long-term comparison between medical and surgical therapies; a superior efficacy of STN-DBS was observed on motor disability, while no significant differences were observed in the progression of motor symptoms and, apart from phonemic verbal fluency, of neuropsychological alterations.
Journal of neurology, neurosurgery, and psychiatry 07/2013; · 4.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although peripheral neuropathies (PN) have been described in patients with Parkinson's disease (PD) treated with oral dopaminergic therapies, anecdotal reports of subacute severe PN have been reported during treatment with enteral levodopa/carbidopa infusion (Duodopa).
We prospectively assessed clinical and electrophysiological data of 15 consecutive patients with PD treated with Duodopa for a mean follow-up of 9 months.
Nerve conduction studies and a clinical evaluation with a standardized battery of peripheral neuropathy scales were performed at baseline and after a mean follow-up of 9 months.
At baseline, mild signs of PN were observed in three subjects, and vitamin B12 serum levels were found to correlate with the amplitude of sural sensory action potentials. Follow-up data were available for 10/15 subjects: one patient developed a subacute sensory-motor PN and three subjects with pre-existing PN showed a moderate worsening of electrophysiological and clinical features. Subclinical electrophysiological alterations of peripheral nerves were observed in two subjects. No significant changes were observed in vitamin B12, folate, homocysteine and methylmalonic acid levels.
In this consecutive series of patients treated with Duodopa, we observed one subacute sensory-motor PN and few length-dependent alterations of peripheral nerves, similar to those described during oral levodopa treatment.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) represents a valid therapeutic option for advanced Parkinson's disease (PD), leading to a significant amelioration of motor fluctuations and levodopa-induced involuntary movements (IM). This study address the issue of whether stimulation frequency may influence the control of IM in STN-DBS treated patients, comparing the effects of 80 Hz and 130 Hz STN-DBS frequencies in 10 parkinsonian patients with residual IM (dyskinesia in 6 cases and dystonia in 4 cases). METHODS: Patients were evaluated by means of the Rush Dyskinesias Rating Scale (blinded-video analysis) and Unified Parkinson's Disease Rating Scale at 4 different time-points: baseline, shortly after the switch of stimulation frequency from 130 Hz to 80 Hz, after 1 month and 12 months of chronic 80 Hz stimulation. RESULTS: IM improved in most subjects after the switch of stimulation frequency: dyskinesias improved in 6/6 subjects and dystonic features in 3/4 subjects after one month of 80 Hz stimulation. However, the 130 Hz STN stimulation was restored in 4 subjects during the following months, because of a gradual worsening of parkinsonian symptoms. A sustained efficacy on motor features and IM was observed with 80 Hz stimulation frequency in the remaining patients. CONCLUSIONS: In this limited cohort of STN-DBS patients, we observed an improvement of residual IM after the switch of stimulation frequency from 130 Hz to 80 Hz. However, a moderate worsening of parkinsonian symptoms was observed in a portion of patients, requiring to return at 130 Hz STN-DBS.
Parkinsonism & Related Disorders 02/2013; · 4.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Sleep disorders are common in patients with advanced Parkinson's disease (PD). Nocturnal akinesia and sleep fragmentation frequently coexist with daytime sleepiness, influencing daytime functioning. Levodopa/carbidopa intestinal gel (LCIG) infusion has been shown to improve motor complications in advanced PD, and preliminary findings suggest that sleep might improve following LCIG infusion. OBJECTIVE: To analyze the impact of LCIG infusion on sleep symptoms and daytime sleepiness in patients with PD. METHODS: Twelve consecutive patients with PD completed the PD-Sleep-Scale-version-2 (PDSS-2) and the Epworth-Sleepiness-Scale (ESS) at baseline and after 2-4 months of LCIG treatment. Activities of daily living, motor symptoms and complications were assessed with the Unified-PD-rating-Scale section II, III, and IV. RESULTS: Nocturnal sleep improved substantially in all patients switched to LCIG infusion. PDSS-2 total score and subscores for 'Disturbed sleep', 'Motor symptoms at night', and 'PD symptoms at night' were significantly reduced. ESS measures of daytime sleepiness also improved. Motor complications and activities of daily living improved significantly with LCIG. CONCLUSION: Subjective measures of sleep quality and daytime sleepiness improve in patients with advanced PD undergoing LCIG infusion. Further studies with a larger number of patients and polysomnographic recordings are needed to confirm the beneficial effect on sleep and clarify the underlying mechanisms.
[Show abstract][Hide abstract] ABSTRACT: The placebo effect, or response, is a complex phenomenon whereby an inert treatment can induce a therapeutic benefit if the subject is made to believe that it is effective. One of the main mechanisms involved is represented by expectations of clinical improvement which, in turn, have been found to either reduce anxiety or activate reward mechanisms. Therefore, the study of the placebo effect allows us to understand how emotions may affect both behavior and therapeutic outcome. The high rate of placebo responders in clinical trials of Parkinson’s disease provided the motivation to investigate the biological underpinnings of the placebo response in Parkinsonian patients. The placebo effect in Parkinson’s disease is induced through the administration of an inert substance which the patient believes to improve motor performance. By using this approach, different behavioral and neuroimaging studies have documented objective improvements in motor performance and an increase of endogenous dopamine release in both the dorsal and ventral striatum. Recently, single neuron recording from the subthalamic and thalamic regions during the implantation of electrodes for deep brain stimulation has been used to investigate the firing pattern of different neurons before and after placebo administration. The results show that the subthalamic nucleus, the substantia nigra pars reticulata, and the ventral anterior thalamus are all involved in the placebo response in Parkinson patients, thus making intraoperative recording an excellent model to characterize the neuronal circuit that is involved in the placebo response in Parkinson’s disease as well as in other disorders of movement.