Neuropsychiatric disturbances in atypical Parkinsonian disorders

Multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) are the most common atypical parkinsonisms. These disorders are characterized by varying combinations of autonomic, cerebellar and pyramidal system, and cognitive dysfunctions. In this paper, we reviewed the evidence available on the presence and type of neuropsychiatric disturbances in MSA, PSP, and CBD. A MedLine, Excerpta Medica, PsycLit, PsycInfo, and Index Medicus search was performed to identify all articles published on this topic between 1965 and 2018. Neuropsychiatric disturbances including depression, anxiety, agitation, and behavioral abnormalities have been frequently described in these disorders, with depression as the most frequent disturbance. MSA patients show a higher frequency of depressive disorders when compared to healthy controls. An increased frequency of anxiety disorders has also been reported in some patients, and no studies have investigated apathy. PSP patients may have depression, apathy, disinhibition, and to a lesser extent, anxiety and agitation. In CBD, neuropsychiatric disorders are similar to those present in PSP. Hallucinations and delusions are rarely reported in these disorders. Neuropsychiatric symptoms in MSA, PSP, and CBD do not appear to be related to the severity of motor dysfunction and are one of the main factors that determine a low quality of life. The results suggest that neuropsychiatric disturbances should always be assessed in patients with atypical parkinsonisms

Quality of life in Parkinson’s disease: Italian validation of the Parkinson’s Disease Questionnaire (PDQ-39-IT)

Translation and cross-cultural adaptation of the 39-item Parkinson’s Disease Questionnaire (PDQ-39) to the Italian culture was performed by Oxford University Innovation in 2008, but this version has never been validated. Therefore, we performed the process of validation of the Italian version of the PDQ-39 (PDQ-39-IT) following the “Consensus-Based Standards for the Selection of Health Status Measurement Instruments” checklist. The translated PDQ-39-IT was tested with 104 patients diagnosed with Parkinson’s disease (PD) who were recruited between June and October 2017. The mean age of the participants was 65.7 ± 10.2 years, and the mean duration of symptoms was 7.4 ± 5.3 years. The internal consistency of the PDQ-39-IT was assessed by Cronbach’s alpha and ranged from 0.69 to 0.92. In an assessment of test-retest reliability in 35 of the 104 patients, the infraclass correlation coefficient (ICC) ranged from 0.85 to 0.96 for the various subitems of the PDQ-39-IT (all p < 0.01). Spearman’s rank correlation coefficient for the validity of the PDQ-39-IT and the Italian version of the 36-Item Short Form (SF-36) was − 0.50 (p < 0.01). The results show that the PDQ-39-IT is a reliable and valid tool to assess the impact of PD on functioning and well-being. Thus, the PDQ-39-IT can be used in clinical and research practice to assess this construct and to evaluate the overall effect of different treatments in Italian PD patients

Reliability and validity of the geriatric depression scale in Italian subjects with Parkinson's disease

Introduction. The Geriatric Depression Scale (GDS) is commonly used to assess depressive symptoms, but its psychometric properties have never been examined in Italian people with Parkinson's disease (PD). The aim of this study was to study the reliability and validity of the Italian version of the GDS in a sample of PD patients. Methods. The GDS was administered to 74 patients with PD in order to study its internal consistency, test-retest reliability, construct, and discriminant validity. Results. The internal consistency of GDS was excellent (α = 0.903), as well as the test-retest reliability (ICC = 0.941 [95% CI: 0.886-0.970]). GDS showed a strong correlation with instruments related to the depression (ρ = 0.880) in PD (ρ = 0.712) and a weak correlation with generic measurement instruments (-0.320 < ρ <-0.217). An area under the curve of 0.892 (95% CI 0.809-0.975) indicated a moderate capability to discriminate depressed patients to nondepressed patient, with a cutoff value between 15 and 16 points that predicts depression (sensitivity = 87%; specificity = 82%). Conclusion. The GDS is a reliable and valid tool in a sample of Italian PD subjects; this scale can be used in clinical and research contexts

Parkinson's disease: autoimmunity and neuroinflammation

Parkinson's disease is a neurodegenerative disease that causes the death of dopaminergic neurons in the substantia nigra. The resulting dopamine deficiency in the basal ganglia leads to a movement disorder that is characterized by classical parkinsonian motor symptoms. Parkinson's disease is recognized as the most common neurodegenerative disorder after Alzheimer's disease. PD ethiopathogenesis remains to be elucidated and has been connected to genetic, environmental and immunologic conditions. The past decade has provided evidence for a significant role of the immune system in PD pathogenesis, either through inflammation or an autoimmune response. Several autoantibodies directed at antigens associated with PD pathogenesis have been identified in PD patients. This immune activation may be the cause of, rather than a response to, the observed neuronal loss. Parkinsonian motor symptoms include bradykinesia, muscular rigidity and resting tremor. The non-motor features include olfactory dysfunction, cognitive impairment, psychiatric symptoms and autonomic dysfunction. Microscopically, the specific degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, which are brain deposits containing a substantial amount of α-synuclein, have been recognized. The progression of Parkinson's disease is characterized by a worsening of motor features; however, as the disease progresses, there is an emergence of complications related to long-term symptomatic treatment. The available therapies for Parkinson's disease only treat the symptoms of the disease. A major goal of Parkinson's disease research is the development of disease-modifying drugs that slow or stop the neurodegenerative process. Drugs that enhance the intracerebral dopamine concentrations or stimulate dopamine receptors remain the mainstay treatment for motor symptoms. Immunomodulatory therapeutic strategies aiming to attenuate PD neurodegeneration have become an attractive option and warrant further investigation

A federal union for dealing with the Russian war

Which models of EU polity for dealing with the Russian war can be derived from the Conference on the Future of Europe? Considering the ‘Report on the Final Outcome’ of the Conference, we traced three models: the parliamentary union, the intergovernmental union and the economic community. Because they appear unable to deal with the consequences of the Russian invasion of Ukraine, this policy brief outlines the contours of an alternative model, the federal union. A description of the Conference on the Future of Europe appears in the factbox

Tools to assess the quality of life in patients with Parkinson’s disease. A systematic review

Introduction . The clinical, social, and economic implications of Parkinson’s disease (PD) are significant; disability occurs leading to a low quality of life (QoL). Information on the QoL of patients with PD and studies on the relationship between QoL and motor and cognitive function are necessary for both research and clinical use to make informed decisions in healthcare and rehabilitation. The aim of this study was to determine which scales are most used to assess QoL in patients with PD. Area covered . A literature search was conducted in MEDLINE, Scopus, CINAHL, PsycINFO, and Web of Science. Two authors independently identified eligible studies based on predefined inclusion criteria and extracted the data. Study quality and the risk of bias were assessed using the COSMIN checklist. Expert opinion . 116 suitable studies were included, and 42 different instruments were identified. The most frequently used scales were the 39-items and 8-items Parkinson’s Disease Questionnaire (PDQ-39) (PDQ-8). These findings suggest further investigation of existing PD outcome measures would benefit patients, researchers, and clinicians. Validated, universal outcome measures are required to allow comparisons across practice; therefore, we recommend that future researchers use a common set of outcome assessments based on the results of this review

Effective connectivity abnormalities in Lewy body disease with visual hallucinations

Objective: To assess the changes in effective connectivity of important regions of the visual network (VIS) and dorsal attention network (DAN) underlying visual hallucinations (VHs) in Dementia with Lewy Bodies (DLB), Parkinson's Disease (PD) and Parkinson's Disease Dementia (PDD), as measured by a transcranial magnetic stimulation-electroencephalographic technique (TMS-EEG). Methods: We stimulated the right visual cortex (V1/V2), the right intraparietal sulcus and the right frontal eye fields, two key regions of the DAN, and measured TMS-evoked cortical activation within the VIS and the DAN. We compared 11 patients with VHs and 15 patients without VHs.Results: Patients with VHs showed lower TMS-evoked cortical activation within the DAN following intraparietal sulcus and frontal eye fields stimulation than patients without VHs. No difference was found between patients with and without cognitive impairment. Also, when considering only patients with cognitive impairment, VHs were associated with lower TMS-evoked cortical activation following intraparietal sulcus stimulation.Conclusions: DLB, PD, and PDD patients with VHs had less effective connectivity of the right intraparietal sulcus within the DAN than patients without VHs. Significance: We provided the first evidence that VHs are associated with specific intraparietal sulcus dysfunction within the DAN in patients with PDD, PD, and DLB.(c) 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Distal Upper Limb Tremor during Walking in Parkinson's Disease

Background: Distal upper limb tremor during walking (TW) is frequently observed in Parkinson's disease (PD) but its clinical features are unknown. Objective: To characterize the occurrence and the clinical features of TW in comparison to the other types of tremors in PD. Methods: Fifty-one PD patients with rest tremor were evaluated off- and on-treatment. Occurrence, body distribution, severity and latency of TW and of other tremor types were assessed. Results: TW was present in 78% of the PD patients examined. TW body distribution and severity were similar to those of rest and re-emergent tremor but different from the postural tremor presented by the same patients. TW latency, observed in 85% of patients, was on average 5.8 s. Dopaminergic treatment significantly improved TW, rest, and re-emergent tremor severity but left TW latency unaffected. Conclusions: TW is a frequent motor sign in PD and is likely a clinical variant of rest tremor

Objective assessment of the effects of opicapone in Parkinson’s disease through kinematic analysis

BackgroundOpicapone (OPC) is a third-generation, selective peripheral COMT inhibitor that improves peripheral L-DOPA bioavailability and reduces OFF time and end-of-dose motor fluctuations in Parkinson's disease (PD) patients.ObjectivesIn this study, we objectively assessed the effects of adding OPC to L-DOPA on bradykinesia in PD through kinematic analysis of finger movements.MethodsWe enrolled 20 treated patients with PD and motor fluctuations. Patients underwent two experimental sessions (L-DOPA, L-DOPA + OPC), separated by at least 1 week. In each session, patients were clinically evaluated and underwent kinematic movement analysis of repetitive finger movements at four time points: (i) before their usual morning dose of L-DOPA (T0), (ii) 30 min (T1), (iii) 1 h and 30 min (T2), and (iv) 3 h and 30 min after the L-DOPA intake (T3).ResultsMovement velocity and amplitude of finger movements were higher in PD patients during the session with OPC compared to the session without OPC at all the time points tested. Importantly, the variability of finger movement velocity and amplitude across T0-T3 was significantly lower in the L-DOPA + OPC than L-DOPA session.ConclusionsThis study is the first objective assessment of the effects of adding OPC to L-DOPA on bradykinesia in patients with PD and motor fluctuations. OPC, in addition to the standard dopaminergic therapy, leads to significant improvements in bradykinesia during clinically relevant periods associated with peripheral L-DOPA dynamics, i.e., the OFF state in the morning, delayed-ON, and wearing-OFF periods