Investigating the Brain Mechanisms of Externally Cued Sit-to-Stand Movement in Parkinson's Disease.

BACKGROUND: One of the more challenging daily-life actions for Parkinson's disease patients is starting to stand from a sitting position. Parkinson's disease patients are known to have difficulty with self-initiated movements and benefit from external cues. However, the brain processes underlying external cueing as an aid remain unknown. The advent of mobile electroencephalography (EEG) now enables the investigation of these processes in dynamic sit-to-stand movements. OBJECTIVE: To identify cortical correlates of the mechanisms underlying auditory cued sit-to-stand movement in Parkinson's disease. METHODS: Twenty-two Parkinson's disease patients and 24 healthy age-matched participants performed self-initiated and externally cued sit-to-stand movements while cortical activity was recorded through 32-channel mobile EEG. RESULTS: Overall impaired integration of sensory and motor information can be seen in the Parkinson's disease patients exhibiting less modulation in the θ band during movement compared to healthy age-matched controls. How Parkinson's disease patients use external cueing of sit-to-stand movements can be seen in larger high ß power over sensorimotor brain areas compared to healthy controls, signaling sensory integration supporting the maintenance of motor output. This appears to require changes in cognitive processing to update the motor plan, reflected in frontal θ power increases in Parkinson's disease patients when cued. CONCLUSION: These findings provide the first neural evidence for why and how cueing improves motor function in sit-to-stand movement in Parkinson's disease. The Parkinson's disease patients' neural correlates indicate that cueing induces greater activation of motor cortical areas supporting the maintenance of a more stable motor output, but involves the use of cognitive resources to update the motor plan. © 2024 International Parkinson and Movement Disorder Society.

Deep brain stimulation of globus pallidus internus and subthalamic nucleus in Parkinson's disease: a multicenter, retrospective study of efficacy and safety.

BACKGROUND: Deep brain stimulation (DBS) is an established therapeutic option in advanced Parkinson's disease (PD). Literature data and recent guidelines remain inconclusive about the best choice as a target between the subthalamic nucleus (STN) and the globus pallidus internus (GPi). MATERIALS AND METHODS: We retrospectively reviewed the clinical efficacy outcomes of 48 DBS-implanted patients (33 STN-DBS and 15 GPi-DBS) at a short- (<1 year from the surgery) and long-term (2-5 years) follow-up. Also, clinical safety outcomes, including postoperative surgical complications and severe side effects, were collected. RESULTS: We found no difference between STN-DBS and GPi-DBS in improving motor symptoms at short-term evaluation. However, STN-DBS achieved a more prominent reduction in oral therapy (L-DOPA equivalent daily dose, P = .02). By contrast, GPi-DBS was superior in ameliorating motor fluctuations and dyskinesia (MDS-UPDRS IV, P < .001) as well as motor experiences of daily living (MDS-UPDRS II, P = .03). The greater efficacy of GPi-DBS on motor fluctuations and experiences of daily living was also present at the long-term follow-up. We observed five serious adverse events, including two suicides, all among STN-DBS patients. CONCLUSION: Both STN-DBS and GPi-DBS are effective in improving motor symptoms severity and complications, but GPi-DBS has a greater impact on motor fluctuations and motor experiences of daily living. These results suggest that the two targets should be considered equivalent in motor efficacy, with GPi-DBS as a valuable option in patients with prominent motor complications. The occurrence of suicides in STN-treated patients claims further attention in target selection.

Pneumocephalus in subthalamic deep brain stimulation for Parkinson's disease: a comparison of two different surgical techniques considering factors conditioning brain shift and target precision.

BACKGROUND: Precise placement of electrodes in deep brain stimulation (DBS) may be influenced by brain shift caused by cerebrospinal fluid leaking or air inflow. We compared accuracy and treatment outcomes between a standard technique and one aiming at reducing brain shift. METHODS: We retrospectively reviewed 46 patients (92 targets) treated with bilateral subthalamic-DBS for Parkinson's disease. The patients were divided into two groups: group A surgery was performed in supine position with standard burr hole, dural opening, fibrin glue and gelfoam plugging. Group B patients were operated in a semi-sitting position with direct dural puncture to reduce CSF loss. We analysed target deviation on head CT performed immediately after surgery and at 1 month merged with preoperative MRI planning. We recorded pneumocephalus volume, brain atrophy and target correction by intraoperative neurophysiology (ION). RESULTS: In group A, the mean pneumocephalus volume was 10.55 cm3, mean brain volume 1116 cm3, mean target deviation 1.09 mm and ION corrected 70% of targets. In group B, mean pneumocephalus was 7.60 cm3 (p = 0.3048), mean brain volume 1132 cm3 (p = 0.6526), mean target deviation 0.64 mm (p = 0.0074) and ION corrected 50% of targets (p = 0.4886). Most leads' deviations realigned to the planned target after pneumocephalus reabsorbtion suggesting a deviation caused by displacement of anatomical structures due to brain shift. Definitive lead position was always decided with ION. CONCLUSIONS: The modified DBS technique significantly reduced errors of electrode placement, though such difference was clinically irrelevant. ION corrected a high amount of trajectories in both groups (70% vs 50%). The choice of either strategy is acceptable.

Subthalamic Stimulation Improves Quality of Life of Patients Aged 61 Years or Older With Short Duration of Parkinson's Disease.

OBJECTIVE: The optimal timing of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) is a topic of ongoing debate. In patients with short disease duration an improvement of quality of life (QoL) has been demonstrated for patients aged younger than 61 years. However, this has not been systematically investigated in older patients yet. We hypothesized that patients aged 61 years or older experience a significant QoL improvement after STN-DBS with no difference in effect sizes for groups of patients with short and longer disease duration. MATERIALS AND METHODS: From four centers (Cologne, London, Manchester, Venice) we identified "older patients" aged 61 years or older with short (≤8 years) or longer disease duration and compared QoL, motor impairment, complications, medication requirements, and Mini-Mental State Examination (MMSE) on baseline and five months after surgery. RESULTS: Mean age/disease duration in 21 subjects with shorter disease duration were 65.5/6.3 years compared to 66.8/14.6 in 33 subjects with longer disease duration. The short disease duration group was affected by less baseline motor complications (p = 0.002). QoL in the short/longer disease duration group improved by 35/20% (p = 0.010/p = 0.006), motor complications by 40/44% (p = 0.018/p < 0.001), and medication requirements by 51/49% (both p < 0.001). MMSE remained unchanged in both groups. CONCLUSION: Patients aged 61 years or older benefited from STN-DBS regardless of short (≤8 years) or longer (>8 years) disease duration. Our results contribute to the debate about DBS selection criteria and timing and call for prospective confirmation in a larger cohort.

Patterns of cortical thickness associated with impulse control disorders in Parkinson's disease.

Previous functional neuroimaging studies in Parkinson's disease (PD) patients with impulse control disorders (ICDs) demonstrated dysfunction of the reward network, although the extent of anatomical changes is unclear. The aim of this study was to measure brain cortical thickness and subcortical volumes, and to assess their relationship with presence and severity of symptoms, in PD patients with and without ICDs. We studied 110 PD patients (N=58 with ICDs) and 33 healthy controls (all negative for ICDs) who underwent an extensive neurological, neuropsychological, and behavioral assessment as well as structural 1.5 Tesla magnetic resonance imaging (MRI). Between-group differences in brain cortical thickness and subcortical volumes, assessed with the FreeSurfer 5.1 tool, were analyzed. In patients with ICDs, we found significant cortical thinning in fronto-striatal circuitry, specifically in the right superior orbitofrontal, left rostral middle frontal, bilateral caudal middle frontal region, and corpus callosum, as well as volume reduction in the right accumbens and increase in the left amygdala. Finally, we observed a positive association relationship between severity of impulsive symptoms and left rostral middle frontal, inferior parietal, and supramarginal areas. These results support the involvement of both reward and response inhibition networks in PD patients with ICDs. Moreover, their severity is associated with alterations in brain regions linked with reward and top-down control networks. Increased understanding of the mechanisms underlying impulsive and compulsive behaviors might help improve therapeutic strategies for these important disorders.

Levodopa-carbidopa intrajejunal gel in advanced Parkinson disease with "on" freezing of gait.

Freezing of gait is a common and disabling disorder in advanced Parkinson's disease (PD). The relationship with dopaminergic medication is complex and often non-linear, thus freezing may occur even when the core parkinsonian features (tremor, rigidity and bradykinesia) appear optimally controlled. We evaluated the effect of Levodopa-carbidopa intrajejunal gel in a group of seven non-demented PD patients with prominent episodes of freezing refractory to adjustments of oral therapy. Clinical assessments were performed in the best "on" state before starting Levodopa-carbidopa intrajejunal gel, while patients were on their standard oral Levodopa (O-LD), and infusion treatment. The main outcome measures were change in freezing of gait (FOG) Questionnaire and UPDRS motor score. FOG Questionnaire and UPDRS subscores related to gait and postural stability significantly improved during Levodopa-carbidopa intrajejunal gel infusion in all patients compared to O-LD treatment. In four out of seven patients, the Levodopa-carbidopa intrajejunal gel dose was equivalent or slightly higher but in three patients was lower compared to O-LD dose recorded at baseline visit. In selected patients, Levodopa-carbidopa intrajejunal gel may improve freezing refractory to oral dopaminergic therapy.

The MTHFR C677T polymorphism modifies age at onset in Parkinson's disease.

Hyperhomocysteinemia is a risk factor for Parkinson's disease (PD) and may result from genetic mutations or/and environmental factors. 5,10-methylenetetrahydrofolate reductase (MTHFR) is a folate-dependent enzyme that catalyzed remethylation of homocysteine (Hcy) and the MTHFR C677T polymorphism makes the MTHFR enzyme thermolabile causing hyperhomocysteinemia. In this study we analyzed whether two functional polymorphisms of MTHFR gene, A1298C and C677T, affect age of onset in PD. We enrolled 120 patients with sporadic PD. Patients were divided into three groups based on MTHFR C677T polymorphisms: (a) homozygotes wild type (CC) (b) heterozygotes (CT) and (c) homozygotes carriers of mutation (TT). MTHFR SNPs were analyzed using High-Resolution Melt analysis and ANOVA was performed to assess whether polymorphisms of MTHFR gene could influence age of onset. The MTHFR A1298C polymorphism had no effect on PD age at onset (p = 1.0) while there was a significant association with MTHFR C677T (p = 0.019 Bonferroni-adjusted post hoc) showing an earlier onset in CC as compared with TT. (p = 0.024). No differences were found for vascular load assessed with magnetic resonance imaging, pharmacological therapy and cognitive state for two MTHFR SNPs. Our results suggest a possible association of MTHFR C677T with age at onset of PD and may have important implications regarding the role of MTHFR.

Advanced Parkinson's disease treatment patterns in Italy: an observational study interim analysis.

BACKGROUND: Oral levodopa remains the mainstay of treatment for Parkinson's disease (PD). However, as PD progresses, response to treatment may fluctuate. Managing fluctuations can be demanding for clinicians and patients. There is a paucity of real-world studies reporting on PD management in patients with fluctuations in treatment response, especially in patients with advanced stages of PD. The multicentre, observational Parkinson's Disease Fluctuations treatment PAthway (PD-FPA) study describes the real-life management of response fluctuations in Italian patients with advanced PD. PATIENTS AND METHODS: PD-FPA had a retrospective and prospective phase; herein, retrospective results are presented. Ten Italian centres enrolled patients with a PD diagnosis from 10-15 years prior to study entry (T0) and who had ≥2-year history of fluctuations. Data on patient demographics, medical history, PD stage, fluctuation characteristics, symptoms, and prescribed treatments were collected at T0 and retrospectively (2 years prior to T0) via patient chart review/interview. RESULTS: Overall, 296 patients (60% male, mean age 68 years, 84% with Hoehn and Yahr scores 2-3) were enrolled. At T0, most patients (99.3%) were on oral levodopa therapy. All patients used dopaminergic medications; adjunctive medications included dopamine agonists (56%) and monoamine oxidase B (60%) and catechol-O-methyltransferase enzyme inhibitors (41%). At T0, 51% of patients had changed therapy, with response fluctuations being the most common reason (74%); wearing-off was the most common fluctuation (83%). CONCLUSION: This interim analysis of PD-FPA suggests that adequate levodopa dosing and adjunctive medications can stabilize advanced PD and provide patients with a good quality of life.

Patients with Parkinson's disease (PD) often exhibit fluctuations in their response to oral levodopa; however, real-world studies on the management of these fluctuations are lacking. This planned interim analysis of the real-world, multicentre, observational PD Fluctuations treatment Pathway (PD-FPA) study found that adequate levodopa dosing and adjunctive medications can stabilize Italian patients with advanced PD and improve their quality of life.

Is there room for new non-dopaminergic treatments in Parkinson's disease?

The contribution of non-dopaminergic degeneration to disability in Parkinson's disease (PD) is still debated. It has been argued that no additional advance can be expected in the management of PD by the development of new dopaminergic agents and suggested that future research should mainly focus on therapies targeting the non-dopaminergic systems involved in the pathogenesis of levodopa resistant motor and non-motor symptoms. We believe this is only partially true and the achievement of a stable dopaminergic restoration and modulation of the dopaminergic system is still an important, unmet need of current pharmacological therapies in PD. Currently available oral levodopa and dopamine agonist medications provide insufficient benefit, as the therapeutic window progressively narrows and motor fluctuations eventually develop in most patients. Conversely, the application of infusion and surgical therapies is limited by selective indications and possible irreversible adverse events and device-related problems. Research of new, safer and less invasive strategies, able to modulate the dopaminergic circuits, would certainly improve the management of motor complications, and most importantly such treatments would be also beneficial to axial and non-motor symptoms, which are universally regarded as the major cause of PD functional disability. Indeed, gait and balance problems may improve with dopaminergic treatment in most patients and they become unresponsive only at the very late stages of the disease. Moreover, several non-motor disturbances, including cognition and depression are often linked to oscillation of dopamine concentrations, and are frequently relieved by treatments providing continuous dopaminergic delivery. Finally, drug trials testing non-dopaminergic treatments for motor and non-motor symptoms of PD provided so far disappointing results. Despite the impressive advances of PD therapeutic strategy, we think there is still need for safe, non-invasive and easily manageable dopaminergic treatments able to provide constant dopamine receptor stimulation and ensure a more stable control of dopamine responsive motor and non-motor symptoms at any stage of the disease.

Diagnostic and screening power of neuropsychological testing in detecting mild cognitive impairment in Parkinson's disease.

Prevalence of mild cognitive impairment (MCI) in Parkinson's disease (PD) is variable likely due to methodological differences in classification criteria and lack of consensus about neuropsychological tests used for cognitive profiling. The main objective of our study was to identify the most suitable neuropsychological tests and determine their screening and diagnostic cutoff scores for PD-MCI. A series of 104 consecutive PD patients performed an extensive neuropsychological evaluation. Individual test values were converted into Z-scores using relative published normative data. According to published criteria, PD patients were categorized as PD-CNT (PD without cognitive impairment), PD-MCI (patients performing -1.5 SDs below the mean score in at least one cognitive domain), and PDD. We used receiver operating characteristic (ROC) curves and K-means clustering analyses to calculate the best discriminating power of each neuropsychological tests in detecting PD-MCI. PD patients were categorized as follows: 55 PD-CNT (53 %), 34 PD-MCI (33 %), and 15 PDD (14 %). PD-MCI had lower education, longer disease duration and greater frequency of hallucinations than PD-CNT. We found that only the Trail Making test, Rey-Osterrieth Complex Figure Test (ROCF) copy, Frontal Assessment Battery (FAB), Digit Span Backward, and Rey's word auditory verbal learning test (RVLT) immediate recall reached significant screening and diagnostic validity in predicting PD-MCI (AUC 0.705-0.795) with cutoff scores calculated by ROC analyses lying within normal range for normative data. Specific neuropsychological tests covering verbal memory, attention/set-shifting, and visual-spatial deficits are the best predictors of MCI in PD if valid cutoff scores are used. These results have consequences for cognitive diagnosis and potentially in establishing the rate of PD cognitive decline.

Validation of the Italian version of the Movement Disorder Society--Unified Parkinson's Disease Rating Scale.

The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been available in English since 2008. As part of this process, the MDS-UPDRS organizing team developed guidelines for development of official non-English translations. We present here the formal process for completing officially approved non-English versions of the MDS-UPDRS and specifically focus on the first of these versions in Italian. The MDS-UPDRS was translated into Italian and tested in 377 native-Italian speaking PD patients. Confirmatory and exploratory factor analyses determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Italian translation. To be designated an 'Official MDS translation,' the Comparative Fit Index (CFI) had to be ≥0.90 relative to the English-language version. For all four parts of the Italian MDS-UPDRS, the CFI, in comparison with the English-language data, was ≥0.94. Exploratory factor analyses revealed some differences between the two datasets, however these differences were considered to be within an acceptable range. The Italian version of the MDS-UPDRS reaches the criterion to be designated as an Official Translation and is now available for use. This protocol will serve as outline for further validation of this in multiple languages.

Characterizing neurocognitive impairments in Parkinson's disease with mobile EEG when walking and stepping over obstacles.

The neural correlates that help us understand the challenges that Parkinson's patients face when negotiating their environment remain under-researched. This deficit in knowledge reflects the methodological constraints of traditional neuroimaging techniques, which include the need to remain still. As a result, much of our understanding of motor disorders is still based on animal models. Daily life challenges such as tripping and falling over obstacles represent one of the main causes of hospitalization for individuals with Parkinson's disease. Here, we report the neural correlates of naturalistic ambulatory obstacle avoidance in Parkinson's disease patients using mobile EEG. We examined 14 medicated patients with Parkinson's disease and 17 neurotypical control participants. Brain activity was recorded while participants walked freely, and while they walked and adjusted their gait to step over expected obstacles (preset adjustment) or unexpected obstacles (online adjustment) displayed on the floor. EEG analysis revealed attenuated cortical activity in Parkinson's patients compared to neurotypical participants in theta (4-7 Hz) and beta (13-35 Hz) frequency bands. The theta power increase when planning an online adjustment to step over unexpected obstacles was reduced in Parkinson's patients compared to neurotypical participants, indicating impaired proactive cognitive control of walking that updates the online action plan when unexpected changes occur in the environment. Impaired action planning processes were further evident in Parkinson's disease patients' diminished beta power suppression when preparing motor adaptation to step over obstacles, regardless of the expectation manipulation, compared to when walking freely. In addition, deficits in reactive control mechanisms in Parkinson's disease compared to neurotypical participants were evident from an attenuated beta rebound signal after crossing an obstacle. Reduced modulation in the theta frequency band in the resetting phase across conditions also suggests a deficit in the evaluation of action outcomes in Parkinson's disease. Taken together, the neural markers of cognitive control of walking observed in Parkinson's disease reveal a pervasive deficit of motor-cognitive control, involving impairments in the proactive and reactive strategies used to avoid obstacles while walking. As such, this study identified neural markers of the motor deficits in Parkinson's disease and revealed patients' difficulties in adapting movements both before and after avoiding obstacles in their path.

Hardware-related infections after deep brain stimulation surgery: review of incidence, severity and management in 212 single-center procedures in the first year after implantation.

BACKGROUND: Device-related infection is a common occurrence after deep brain stimulation (DBS) surgery, and may result in additional interventions and a loss of efficacy of therapy. This retrospective review aimed to evaluate the incidence, severity and management of device-related infections in 212 DBS procedures performed in our institute. METHODS: Data on 106 patients, in whom 212 DBS procedures were performed between 2001 and 2011 at our institute by a single neurosurgeon (M.P.), were reviewed to assess the incidence, severity, management and clinical characteristics of infections in the first year after the implantation of a DBS system. RESULTS: Infections occurred in 8.5% of patients and 4.2% of procedures. Of the nine infections, eight involved the neurostimulator and extensions, and one the whole system. The infections occurred 30.7 days after implantation: 7 within 30 days and 2 within 6 months. Infected and uninfected patients were comparable in terms of age, sex, indication for DBS implantation and neurostimulator location. In eight cases, the system components involved were removed and re-implanted after 3 months, while in one case the complete hardware was removed and not re-implanted. CONCLUSION: The overall incidence of postoperative infections after DBS system implantation was 4.2%; this rate decreased over time. All infections required further surgery. Correct and timely management of partial infections may result in successful salvage of part of the system.

Levodopa-carbidopa intrajejunal infusion in Parkinson's disease: untangling the role of age.

OBJECTIVES: Levodopa-Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson's disease (PD). Although age may not be a limiting factor for LCIG implant, no data are available on late elderly PD (LE-PD) subjects. In this cross-sectional, we aimed to demonstrate if older age may impact on quality of life (QoL), motor and non-motor symptoms severity, and profile of side effects in PD treated with LCIG. METHODS: Out of 512 PD subjects treated with LCIG at 9 Italian PD centers, we selected 25 LE-PD defined as age ≥ 80 years at last follow-up who were available to attend the study visit. Twenty-five PD patients (Control-PD, defined as age < 75 years at last follow-up) matched to LE-PD by disease and LCIG duration served as control group. The following motor and non-motor variables were ascertained: quality of life (PDQ-8), time spent in ON, wearing-off Questionnaire, Unified PD Rating Scale, freezing of gait questionnaire, Parkinson's disease sleep scale-2, Non Motor Symptoms Scale (NMSS), and MOCA. RESULTS: No statistically significant differences were found between LE-PD and Control-PD on PDQ-8 and several motor and non-motor variables. LE-PD had less frequent and milder impulsive-compulsive behaviors and milder dyskinesia. At multivariable regression, worse quality of life was associated with UPDRS-III and NMSS scores but not to age at study visit and age at LICG implant. Rate of adverse effects was similar in both groups. Drop-out rate calculated in the whole PD cohort was comparable between the two groups. CONCLUSION: Our data provide evidence that valuable LCIG infusion might be achieved in late elderly PD.

Brain impedance variation of directional leads implanted in subthalamic nuclei of Parkinsonian patients.

OBJECTIVE: Conventional deep brain stimulation (DBS) systems with ring-shaped leads generate spherical electrical fields. In contrast, novel directional leads use segmented electrodes. Aim of this study was to quantify the impedance variations over time in subjects with the directional Cartesia-Boston® system. METHODS: Impedance records, programming settings, and clinical data of 11 consecutive Parkinsonian patients implanted with DBS directional leads in two Italian centers (Udine and Vicenza) were retrospectively evaluated. Data were collected before starting stimulation (in the operating room and at days 5 and 40) and after switching stimulation on at the successive follow-up visits (1, 6 and 12 months). RESULTS: Directional leads have significantly higher impedance than ring leads. Stimulated contacts had always lower impedance compared to non-stimulated contacts. Before DBS-on, all contacts had higher impedance in the operating room, with an initial decrease five days post-surgery and a subsequent increase at day 40, more evident for directional contacts. The impedance of directional leads increased post-implantation at 1 and 6 months with a plateau at 12 months. CONCLUSIONS: There was a significant difference between the directional and ring leads at baseline (before activation of DBS) and during follow-up (chronic DBS). SIGNIFICANCE: Our study reveals new information about the impedance of segmented electrodes that is useful for patient management during the initial test period, as well as during long-term DBS follow-up.

Deep brain stimulation in Parkinson's disease: A multicentric, long-term, observational pilot study.

BACKGROUND: The impact of deep brain stimulation (DBS) on cognitive and urinary disorders, falls, and eventually hospitalizations and mortality in Parkinson's disease (PD) is still debated. OBJECTIVE: We compared the rates of dementia, mild cognitive impairment (MCI), urinary incontinence, nocturia, falls, hospitalizations, and mortality in a cohort of PD patients undergoing DBS with a cohort of medically-treated patients chosen as controls. METHODS: We conducted a retrospective pilot study in six Italian DBS centers. 91 PD patients receiving DBS and 91 age- and gender-matched controls receiving the best medical treatment alone with a minimum follow-up of one year were enrolled. Clinical data were collected from baseline to the last follow-up visit using an ad-hoc developed web-based system. RESULTS: The risk of dementia was similar in the two groups while patients in the surgical cohort had lower rates of MCI, urinary incontinence, nocturia, and falls. In contrast, the risk of hospital admissions related to PD was higher in the surgical cohort. However, when excluding hospitalizations related to DBS surgery, the difference between the two cohorts was not significant. The surgical cohort had a lower number of hospitalizations not related to PD. The risk of death was similar in the two groups. CONCLUSION: Despite a higher risk of hospitalization, patients receiving DBS had a lower rate of MCI, urinary incontinence, nocturia and falls, without evidence of an increased risk of dementia and mortality. Although these findings need to be confirmed in prospective studies, they seem to suggest that DBS may play a significant role in the management of non-motor symptoms and common complications of advanced PD.

[123I]FP-CIT SPET imaging in drug-induced Parkinsonism.

We assessed the status of dopamine nerve terminals in patients treated with dopamine receptor blocking agents (DRBAs) who had developed drug-induced parkinsonism (DIP). We performed [(123)I]FP-CIT SPET in 32 consecutive patients who were on DRBAs for at least 6 months and developed extrapyramidal signs. The UPDRS-III was used to assess clinical severity. Twenty-six age- and sex-matched healthy subjects served as control group. Putamen [(123)I]FP-CIT SPET binding was reduced in 14 and normal in the remaining 18 patients. There was no difference between the two groups for age, duration of DRBAs treatment, UPDRS III, tremor, rigidity, and bradykinesia subscores for upper and lower limbs. Conversely, symmetry of parkinsonian signs and presence bucco-linguo-masticatory dyskinesias were more frequent in individuals with normal tracer binding. Imaging of the dopamine transporter may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals.

Which patients discontinue? Issues on Levodopa/carbidopa intestinal gel treatment: Italian multicentre survey of 905 patients with long-term follow-up.

OBJECTIVES: To report the results of a national survey aimed at quantifying the current level of diffusion of Levodopa/carbidopa intestinal gel (LCIG) in Italy. METHODS: Sixty Parkinson's Disease (PD) specialists in Italy were invited to complete a survey covering issues on clinical and practical aspects of LCIG therapy. RESULTS: Clinical features of 905 patients were collected retrospectively. The majority of centres reported the use of a multidisciplinary team, biochemistry testing, neurophysiological and neuropsychological tests before and after treatment, in addition to caregivers' training and patient's follow as outpatients. Most centres (60%) used internal guidelines for patient selection. The overall rate of adverse events was 55.1%. Weight loss, chronic polyneuropathy and stoma infection were the most frequently reported. 40% of centres used replacement therapy with Vitamin B12 and Folic acid from the start of LCIG and continued this for the duration of treatment. The rate of discontinuation was of 25.7% overall, with 9.5% of cases occurring in the first year. The main causes of withdrawal were device-related complications, disease progression (comorbidity, severe dementia) and caregiver and/or patient dissatisfaction. CONCLUSIONS: In Italy LCIG infusion is managed in a uniform manner at a clinical, practical and organizational level even though the selection criteria are not standardized through the country. The high percentage of patients remaining on treatment in the short- and long-term follow-up confirms effectiveness of treatment, careful follow-up, and appropriate patient and caregivers training.