Advanced Parkinson's Disease Treatment Simplification and Long-Term Outcomes with Levodopa Carbidopa Intestinal Gel: COSMOS Romanian Subanalysis.

The aim of the COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS) was to assess the use of levodopa/carbidopa intestinal gel (LCIG) as monotherapy in patients with advanced Parkinson's disease (APD) in routine clinical practice. COSMOS was an international observational study with one cross-sectional visit and retrospective data collection. In Romania, 95 adult patients with APD on LCIG treatment for at least 12 months were enrolled and stratified according to their LCIG therapy after 12 months: monotherapy (without any add-on PD medication), monotherapy with night PD medication and LCIG + add-on medication. Compared to the moment of LCIG initiation, the percentage of patients on monotherapy increased at three months after LCIG initiation and remained constant up to 12 months, when 30.5% of the patients were on LCIG monotherapy and 11.6% were on monotherapy with night medication. "Off" time and "On" time with dyskinesia decreased from LCIG initiation to patient visit in all groups. LCIG monotherapy with or without night medication may provide a simplified treatment option for selected APD patients, with long-term efficacy similar to that of LCIG plus add-on medication.

Management Challenges of Severe, Complex Dyskinesia. Data from a Large Cohort of Patients Treated with Levodopa-Carbidopa Intestinal Gel for Advanced Parkinson's Disease.

BACKGROUND: In the advanced stages of Parkinson's disease (APD), complex forms of dyskinesia may severely impair the patient's quality of life. OBJECTIVE: In the present study, we aimed to analyze the evolution under LCIG therapy of the most important motor fluctuations and complex disabling dyskinesias, including diphasic dyskinesia. METHODS: In this retrospective study, we analyzed the characteristics of patients with APD who had at least 30 min of diphasic dyskinesia (DID) in 3 consecutive days, were considered responders and were treated with LCIG in our clinic. Patients were evaluated before and after PEG and at 6, 12 and 18 months, when the changes in the therapy were recorded, and they completed a 7-point Global Patient Impression of Improvement (PGI-I) scale. RESULTS: Forty patients fulfilled the inclusion criteria-out of which, 34 performed all visits. There was a substantial difference between the calculated and real LCIG (1232 ± 337 mg vs. 1823 ± 728 mg). The motor fluctuations and most dyskinesias improved significantly after starting LCIG, but an increasing number of patients needed longer daily administrations of LCIG (24 instead of 16 h). CONCLUSIONS: Patients with APD with complex dyskinesias must be tested in dedicated hospitals, and they need a special therapeutic approach. The properly adapted LCIG treatment regarding the dose and time of administration completed with well-selected add-on medication should offer improvement for patients who want to or can only choose this DAT vs. others.

Characterizing Advanced Parkinson's Disease: Romanian Subanalysis from the OBSERVE-PD Study.

OBSERVE-PD was a cross-sectional, multicountry, observational study conducted in 128 Movement Disorders Centers (MDCs) in 18 countries. Overall, the study enrolled 2615 patients. The aim was to determine the proportion of patients with advanced Parkinson's disease (APD) versus non-APD from MDCs and to uncover the clinical burden of APD, as well as a correlation between overall assessment of APD and several indicators of APD. The advanced stage of the disease and severity were assessed by investigators using their clinical judgement. Data were collected during a single visit between February 2015 and January 2016. Agreement on physician judgement of APD diagnosis and fulfillment of at least one previously established APD indicator was calculated. Motor and nonmotor symptoms (NMSs), activities of daily living, treatment complications, quality of life (QoL), conventional treatments, and device-aided therapy (DAT) eligibility were assessed. Here, country-specific results of 161 Romanian patients with PD are presented. In total, 59.0% of patients were diagnosed with APD and 78.8% met at least one APD indicator. There was only moderate agreement between clinical judgement of APD and overall fulfillment of APD indicators. All scores related to motor symptoms, NMSs, and treatment complications, as well as to QoL, showed a higher disease burden for patients with APD versus non-APD. Physicians considered 73.7% of patients with APD eligible for DAT. The majority of patients eligible for DAT (54.3%) did not receive such treatment. Our results highlight the importance of earlier recognition of APD, by combining clinical judgement with more standardized clinical tools, such as generally recognized APD criteria. However, timely diagnosis of APD alone is not enough to improve patient outcomes. Other critical factors include patient acceptance and access to appropriate treatment.

Affective theory of mind in Parkinson's disease: the effect of cognitive performance.

PURPOSE: Among other non-motor symptoms, theory of mind (ToM), the ability to recognize, understand and infer others' mental states, beliefs, intents and wishes, has been shown to deteriorate during the course of Parkinson's disease (PD). It has been speculated that ToM impairments could be related to cognitive deficits in PD. However, the current state of literature suggests that there is heterogeneity regarding the involvement of cognitive functioning in the relationship of PD and ToM. The study aimed to measure affective ToM abilities and cognitive performance in a sample of PD patients, to explore the link between affective ToM abilities and cognitive status, and to examine the impact of PD on affective ToM through the mediator effect of cognitive performance. PATIENTS AND METHODS: Sixty-five patients diagnosed with idiopathic PD and 51 healthy controls matched for age, gender and educational level completed a visual affective ToM task (Reading the Mind in the Eyes - RMET), cognitive performance was evaluated with Montreal Cognitive Assessment, and psychiatric symptoms were measured with BPRS-E (Brief Psychiatric Rating Scale). RESULTS: Affective ToM abilities were preserved in early PD patients, declining as the disease progressed. Deficits in cognitive functioning predicted deficiencies in affective ToM. Although attention (AT), executive functions (EF) and visuospatial abilities (VSA) together mediated the relationship between PD and affective ToM, only VSA impairment had a specific negative impact on affective ToM. Moreover, 41% of the total effect of attention and executive functions on affective ToM was mediated by visuospatial skills. CONCLUSION: Cognitive performance may have an impact on the relationship between PD and affective ToM through the involvement of VSA. The influence of AT and EF in this relationship appears to be also exerted by PD patients' VSA.

Integrative clinico-biological, pharmacogenetic, neuroimagistic, neuroendocrinological and psychological correlations in depressive and anxiety disorders.

We approach the theme of modern treatment strategies, based on clinico-biological, pharmacogenetic, neuroimagistic, neuroendocrinological and psychological integrative correlations in the management of depressive and comorbid anxiety disorders. We target to evaluate the efficacy of the pharmacogenetic testing and the evolution, functioning of patients in correlation with specific neurobiological, neuroimagistic and neuroendocrinological markers. Our research was conducted between 2010-2016 on 80 children and adolescents with depressive and comorbid anxiety disorders - 40 children (G1 group), who benefited in choosing the pharmacotherapy from pharmacogenetic testing and 40 children without testing (G2 group). Also, the patients were evaluated through magnetic resonance (MR) spectroscopy at baseline and after pharmacotherapy. The efficacy of the chosen therapy in correlation with the pharmacogenetic testing was evaluated through the mean change in the CDRS (Children's Depression Rating Scale) total scores, in the CGI-S÷I (Clinical Global Impression - Severity÷Improvement), CGAS (Children's Global Assessment Scale) and through the change of the relevant neurobiological markers and MR spectroscopy metabolites. We evaluated the side effects through the PAERS (Pediatric Adverse Events Rating Scale)-Clinician. Our results show statistically significant differences of the clinical scores between the studied groups: for those subjects who benefited of pharmacogenetic testing, the CDRS, the global functioning scores prove a higher clinical improvement, a better compliance and lower PAERS side effects scores and also improvement concerning the MR spectroscopy dosed metabolites values. Our research was a proof sustaining the use of the pharmacogenetic testing in clinical practice and the value of investigating relevant neurobiological, neuroimagistic and neuroendocrinological markers for a personalized therapy in depressive disorders.

The effect of neurobiological changes in the brain of children with schizophrenia, ultra high-risk for psychosis and epilepsy: clinical correlations with EEG and neuroimagistic abnormalities.

Relatively little research has been conducted on quantitative electroencephalography (QEEG) activity in patients with psychosis÷schizophrenia, especially in populations at-risk for the illness. Further studies are needed, in order to offer a possible endophenotypic marker of the cerebral functioning, associated with psychosis÷schizophrenia, in correlation with the neuroimaging, the neurocognitive, biochemical, molecular genetic tests, clinical aspects and the EEG activity from the same subjects. The aim was to investigate the role the QEEG abnormalities play in the etiology of psychosis÷schizophrenia, whether it can provide an endophenotype for psychosis and to make some correlations with the results obtained through magnetic resonance (MR) spectroscopy, for proper early detection and intervention. The prospective research was performed in the University Clinic of Child and Adolescent Psychiatry, Timisoara, Romania, involving 55 children with schizophrenia or ultra high-risk (UHR) for psychosis (groups 1, 2, 3 and 4) and 55 children as healthy controls (group 5). Groups 1 and 2 (28 children) are diagnosed with schizophrenia, groups 3 and 4 are UHR for psychosis (27 children), and group 5 represents healthy controls. Groups 1 and 3 had convulsive seizures in their personal history. We noticed: through the QEEG, numerous patterns of theta and delta activity, the diminished amplitude of the alpha band waves and the diminished alpha activity; also, the onset of psychosis was earlier at those presenting convulsive seizures in their personal history (groups 1 and 3); also, specific neuroimagistic abnormalities and modifications. The cerebral lesions, appearing during the development, raise the liability for schizophrenia. The high-risk for schizophrenia is correlated with the personal history of epilepsy, as well as with the family risk for psychosis.