Mantenere attivo un blog dedicato ad un argomento specifico costa fatica e comporta l’utilizzo di risorse che, allo stato, non è possibile sostenere. In attesa di tempi migliori il blog “Neurosal” non verrà aggiornato. Grazie a quanti hanno voluto seguirlo finora.
Learning Processes in Parkinson’s Disease and Healthy Aging
Poster presented by Madeleine Sharp, Karin Foerde, Nathaniel Daw, Daphna Shohamy (New York, NY, USA).
To identify the exact role of dopamine in reward learning and to provide a more specific account of the cognitive dysfunction of PD as it relates to dopamine deficiency.
It is widely accepted that Parkinson’s disease patients have a cognitive learning deficit, which is presumed to be related to the decreased dopamine-dependent learning signal in the striatum. However, the effect of dopamine on cognition likely extends beyond the striatum, to the prefrontal cortex in particular, where it could also support learning through positive effects on executive function that are not accounted for in standard reinforcement learning tasks. These different components of reinforcement learning are hypothesized to occur as two parallel processes. The first, habit (model-free) learning, is exquisitely sensitive to reward and is thought to depend critically on striatal signalling of prediction errors. The second, goal-directed or model-based learning, is also sensitive to feedback but additionally depends on core components of executive function.
We used a two-step sequential decision-making task previously shown to dissociate between these two learning processes and compared PD patients ON and OFF medications to healthy controls to determine the effect of disease and dopaminergic medications on these two learning processes.
We found that PD-OFF had normal model-free learning, which depends entirely on feedback but that they had a model-based learning deficit, which was fully restored by dopamine replacement and the severity of which was correlated with working memory deficit.
First, the simple process of predicting and pursuing reward was intact in PD. Second, our results provide evidence for dopaminergic control of model-based learning and suggest that it is particularly sensitive to the dopamine loss of early to moderate stage Parkinson’s disease.
Impulse Control Disorders are associated with REM Sleep Behavior Disorder in patients with Parkinson’s Disease: a Video-Polysomnographic Study.
Poster presented by Maria Livia Fantini, Maurizio Zibetti, Michela Figorilli, Beudin Patricia,Ana Marques,Debilly Bérangère,Derost Philippe,Miguel Ulla,Nicolas Vitello,Tiphaine Vidal, Monica Puligheddu, Alessandro Cicolin, Leonardo Lopiano, Franck Durif
OBJECTIVE: to compare the frequency of REM Sleep Behavior Disorder (RBD) diagnosed by video-polysomnography in patients with Parkinson’s Disease (PD) with and without impulse control disorder (ICDs).
BACKGROUND: in a recent study we have shown that patients with PD and clinical probable RBD have an increased risk to develop symptoms of ICDs as assessed by questionnaire.
METHODS: twenty-six consecutive non-demented PD patients [18M; mean age: 64.9±9.1 yrs., Hohen &Yahr (H&Y):2.2±0.5] with one or more current ICDs (PD-ICDs) were identified during their routine evaluation at two movement disorders centers. The presence of ICDs was assessed through a detailed clinical interview and diagnosis was made according to standard criteria. PD-ICDs patients were matched by sex and age with 26 consecutive PD patients without history of ICDs (PD-noICDs, mean age: 64.3±9.1 yrs, H&Y: 2.3±0.6). All subjects underwent to a full-night video-polysomnographic recording (vPSG). Sleep scoring was performed blindly to ICDs condition and RBD was diagnosed according to ICDS-3 criteria, including a quantified measure of REM sleep without Atonia (RSWA).
RESULTS: RBD was found in 23/26 (88.0%) PD-ICDs patients vs. 13/26 (50.0%) PD-no ICDs patients (Fisher-exact test: p=0.006). Mean RSWA in PD-ICDs and PD-noICDs was 53.6±26.2% and 32.6±28.9% respectively (p=0.04). Two of the three PD-ICDs patients, failing to fulfill the RBD diagnostic criteria, showed very short motor episodes during REM sleep at video-monitoring, possibly suggesting a minor RBD.
CONCLUSION: in the present study, vPSG-diagnosed RBD was found in nearly 90% of PD patients with ICDs and in 50% of the PD-noICDs. These results confirm our previous findings and suggest that RBD might represent a predisposing factor for ICDs in PD.
Incidence of Impulsive and Compulsive Behavior Type Adverse Events with Long-term Rotigotine: A Post-hoc Analysis
Angelo Antonini, Mahnaz Asgharnejad, Lars Bauer, Frank Grieger, Babak Boroojerdi – Padua, Italy; Raleigh, NC, USA; Monheim am Rhein, Germany.
OBJECTIVE: To evaluate the incidence of adverse events (AEs) suggestive of impulsive and compulsive behaviors (ICBs) in studies of long-term rotigotine transdermal patch in patients with Parkinson’s disease (PD).
BACKGROUND: Use of dopamine receptor agonists in patients with PD is associated with the development of impulse control disorders (ICDs) such as pathological gambling, hypersexuality, compulsive shopping, and compulsive eating, and other ICBs such as obsessive compulsive disorder (OCD), punding, and hobbyism. The long-term safety and tolerability of rotigotine has been reported; however, the incidence of ICDs/ICBs reported as AEs with long-term exposure has not been reported.
DESIGN/METHODS: Post-hoc analysis of pooled data from six open-label extension, long-term studies of rotigotine in patients with early or advanced PD (SP516, SP702, SP715, SP716, SP833, SP915). The sub-groups of patients who were treated with rotigotine for ≥6 months and were administered the modified Minnesota Impulse Disorders Interview during the study were included in the analysis. MedDRA version 9.1 was used for coding the AEs, and AEs were selected based on their Preferred Term.
RESULTS: 786 patients met the two above-mentioned criteria and were included in the analysis. Patients had a mean ± SD exposure to rotigotine of 49.36 ± 17.59 months (median: 52.88 months; range: 6.2-74.2 months). A total of 105 ICD/ICB type AEs were reported in 71 (9.0%) patients. The most commonly reported event was OCD (5.3%), followed by pathological gambling (1.7%). There did not appear to be a dose-related increase in the incidence of ICB type AEs with rotigotine.
CONCLUSIONS: In this post-hoc analysis of patients with PD, the overall incidence of ICDs/ICBs reported as AEs during long-term (≥6 months) exposure to rotigotine transdermal patch was 9.0%, and similar to previously reported data. The incidence of ICDs/ICBs with rotigotine did not appear to be dose-dependent.
Cognitive and motor function of orthostatic hypotension patient taking alpha-blocker for benign prostate hypertrophy – Preliminary study
Poster presented by Hee Kwon Park, Jong-Hyun Ahn, JiWon Kwon, Soo-Jeong Kim, Eung-Seok Lee, Cindy Yoon, Eun-Ki Kim, Joung-Ho Rha Incheon, Korea, Republic of.
Objective: To investigate the neurological consequence of alpha-blocker induced orthostatic hypotension (OH) in the benign prostate hypertrophy (BPH) patients.
Background: Alpha-blocker is usually prescribed for BPH management, but adverse effect of OH frequently follows, and its clinical impact has not been well studied.
Design/Method: BPH patients (≥65 years old) who had taken alpha-blocker ≥1 year and agreed on this study were prospectively selected from the urology clinic. Patient with previous history of OH, stroke, or dementia was excluded. For the diagnosis of OH, all patients took head-up tilt table test. Neuropsychological assessment including mini-mental state exam (MMSE) and Montreal cognitive assessment (MoCA), along with motor function assessment by unified Parkinson disease rating scale (UPDRS) were also performed in some patients. MMSE score ≤25 were defined as mild cognitive impairment (MCI). Comparative analysis was made between patients with OH and patients without (control).
Results: From April 2011 to March 2012, total 51 patients (age 69.7±8, all male) were enrolled. Among them, OH was identified in 31 subjects (61%). MCI was diagnosed in 15 and the proportion was not different between OH group and control (32 vs. 25%, p=0.58). However, the OH group showed tendency of more impaired digit forward span than the control (4.9±1.7 vs. 5.7±1.4, p=0.08), which became significant in the older subgroup (≥71y, 4.3±1.2 vs. 5.9±1.2, p=0.01). OH group also showed significantly impaired motor function reflected by much higher UPDRS motor score (14.8±13.5 vs. 3.7±4.8, p=0.02) compared to the control.
Conclusions: Substantial portion of BPH patients taking alpha-blocker develop OH. This “induced” OH had no significant effect on cognitive function, but it might be possibly associated with working memory impairment and motor slowing in the elderly. Further confirmative investigation would be necessary.
Alpha-Synuclein and Autonomic Neuropathy Progression in a Longitudinal Study of Parkinson Disease
Poster presented by Christopher Gibbons, Ningshan Wang, Jenniffer Garcia, Roy Freeman Boston, MA, USA.
OBJECTIVE: To determine the relationship between α-synuclein deposition, autonomic nerve fiber density and autonomic function in a longitudinal study of patients with PD.
BACKGROUND: We recently reported that α-synuclein can be detected within cutaneous autonomic nerve fibers of patients with Parkinson’s disease (PD) (Wang N. Neurology 2013). The long-term implication of this finding on autonomic nerve fiber structure and function is unknown.
DESIGN/METHODS: Twenty-five individuals with PD and 8 age and gender-matched healthy control subjects had clinical examinations, autonomic function testing and skin biopsies from 4 sites taken at an initial visit and repeated 1 year later. Skin biopsies were stained for PGP9.5, and total α-synuclein (both phosphorylated and non-phosphorylated). The ratio of α-synuclein to nerve innervation (α-synuclein ratio) was calculated for each sample. The density of intra-epidermal (IENFD), sudomotor (SGNFD) and pilomotor (PMNFD) nerve fibers was determined. The initial α-synuclein ratio was compared against the change in nerve fiber density (IENFD, SGNFD and PMNFD) over 1 year.
RESULTS: Patients with PD had higher α-synuclein ratios compared to controls within pilomotor nerves and sudomotor nerves at all sites (P<0.01, all biopsy sites). Higher α-synuclein ratios measured at the baseline visit were correlated with a greater decline in SNGFD (r=-0.46, P<0.01) and PMNFD (r=-0.61, P<0.001) 1 year later. There was a correlation between higher α-synuclein ratios and greater decline in heart rate variability (r=0.39, P<0.05), Valsalva Ratio (r=0.42, P<0.05) and orthostatic hypotension (r=0.46, P<0.01).
CONCLUSIONS: These data support the pathophysiologic association between α-synuclein deposition, autonomic nerve fiber degeneration and autonomic dysfunction in individuals with PD. The results of this longitudinal study further support the role of the α-synuclein as a biomarker in patients with Parkinson disease.
Ad oggi non erano presenti in letteratura dati sull’utilizzo della zonisamide nel trattamento dei pazienti parkinsoniani in stadio iniziale. A colmare la lacuna il lavoro pubblicato su Neurology and Clinical Neuroscience (link) che evidenzia un miglioramento sia delle disfunzioni motorie che del sonno nei pazienti non trattati (de novo). Gli effetti benefici del trattamento si sono presentati a 1-2 mesi. Il trattamento, stando ai primi dati, sembrerebbe efficace anche sul sintomo tremore.I