Applying a new version of the Brazilian-Portuguese UPSIT smell test in Brazil

Standardized olfactory tests are now available to quantitatively assess disorders of olfaction. A Brazilian-Portuguese version of the University of Pennsylvania Smell Identification Test (UPSIT) is currently being developed specifically for the Brazilian population. The most recent Brazilian-Portuguese version of the UPSIT (UPSIT-Br2) was administered to 88 Brazilian subjects who had no history of neurological or otorhinolaryngological disease. UPSIT-Br2 scores decreased with age, were lower in men than in women, and were lower in subjects with lower income. The degree to which the poorer performance of subjects with lower socio-economic status reflects lack of familiarity with test items is not known. Although this version of the UPSIT provides a sensitive and useful test of smell function for the Brazilian population, a revision of some test items is needed to achieve comparable norms to those found using the North American UPSIT in the United States

The prevalence of impulsive compulsive behaviors in patients treated with apomorphine infusion: a retrospective analysis

BACKGROUND: Impulsive compulsive behaviors (ICBs) can affect a significant number of Parkinson's disease (PD) patients. OBJECTIVE: We have studied brain samples from a brain bank of PD patients who received apomorphine via continuous infusion in life to assess the prevalence and outcome of ICBs. METHODS: A search on the Queen Square Brain Bank (QSBB) database for cases donated from 2005 to 2016 with a pathological diagnosis of idiopathic PD was conducted. Notes of all donors who used apomorphine via continuous infusion for at least three months were reviewed. Clinical and demographic data were collected, as well as detailed information on treatment, prevalence and outcomes of ICBs. RESULTS: 193 PD cases, 124 males and 69 females, with an average age at disease onset of 60.2 years and average disease duration of 17.2 years were reviewed. Dementia occurred in nearly half of the sample, depression in one quarter, and dyskinesias in a little over 40%. The prevalence of ICBs was 14.5%. Twenty-four individuals used apomorphine infusion for more than three months. Patients on apomorphine had younger age at disease onset, longer disease duration, and higher prevalence of dyskinesias. The prevalence of de novo ICB cases among patients on apomorphine was 8.3%. Apomorphine infusion was used for an average of 63.1 months on an average maximum dose of 79.5 mg per day. Ten patients remained on apomorphine until death. CONCLUSIONS: Apomorphine can be used as an alternative treatment for patients with previous ICBs as it has low risk of triggering recurrence of ICBs

Neuropsychiatric Features of Punding and Hobbyism in Parkinson's Disease

BACKGROUND: Little is known about the cognitive and neuropsychiatric profile associated with punding and hobbyism in Parkinson's disease (PD). OBJECTIVE: To compare the clinical and neuropsychological features of PD patients with punding and hobbyism to PD controls. METHODS: The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) was used as a screening tool, and a structured interview was used to diagnose punding/hobbyism. Clinical and neuropsychological assessment was conducted with validated questionnaires/scales. RESULTS: Twenty-one patients with PD and punding (PD + pu) were compared to 26 with hobbyism (PD + h) and 25 PD controls. PD + pu patients showed higher levels of anxiety, non-motor symptoms and motor symptoms, and lower Frontal Assessment Battery scores. The PD + h group exhibited similar levels of anxiety and motor fluctuations to the PD + pu group. CONCLUSION: PD + pu showed increased anxiety and frontal lobe dysfunction, similar to PD + h. Hobbyism could be a prodromal phase with increased risk of leading to punding

Lower nucleus accumbens α-synuclein load and D3 receptor levels in Parkinson's disease with impulsive compulsive behaviours

Impulsive compulsive behaviours in Parkinson’s disease have been linked to increased dopaminergic release in the ventral striatum and excessive stimulation of dopamine D3 receptors. Thirty-one patients with impulsive compulsive behaviours and Parkinson’s disease who donated their brains to the Queen Square Brain Bank for Neurological Disorders were assessed for α-synuclein neuropathological load and tyrosine hydroxylase levels in the nucleus accumbens, dorsal putamen and caudate using immunohistochemistry. Dopamine D2 and dopamine D3 receptors protein levels in the nucleus accumbens, frontal cortex and putamen were determined using western blotting. Results were compared to 29 Parkinson’s disease cases without impulsive compulsive behaviours matched by age, sex, disease duration, age at Parkinson’s disease onset and disease duration. The majority of patients with impulsive compulsive behaviours had dopamine dysregulation syndrome. Patients with Parkinson’s disease and impulsive compulsive behaviours had lower α-synuclein load and dopamine D3 receptor levels in the nucleus accumbens. No differences were seen between groups in the other brain areas and in the analysis of tyrosine hydroxylase and dopamine D2 receptor levels. Lower α-synuclein load in the nucleus accumbens of individuals with Parkinson’s disease and impulsive compulsive behaviours was confirmed on western blotting. Downregulation of the dopamine D3 receptor levels may have occurred either as a consequence of the degenerative process or of a pre-morbid trait. The lower levels of α-synuclein may have contributed to an excessive stimulation of the ventral striatum resulting in impulsive compulsive behaviours

Macrophages down-regulate gene expression of intervertebral disc degenerative markers under a pro-inflammatory microenvironment

Low back pain is a highly prevalent clinical problem and intervertebral disc (IVD) degeneration is now accepted as the major pathophysiological mechanism responsible for this condition. Accumulating evidence suggests that inflammation plays a crucial role in the progression of human IVD degeneration, with macrophages being pointed as the key immune cell players in this process since their infiltration in degenerated IVD samples has been extensively demonstrated. Since they are highly plastic, macrophages can play different roles depending on the microenvironmental cues. The study of inflammation associated with IVD degeneration has been somehow neglected and one of the reasons is related with lack of adequate models. To overcome this, we established and characterized a new model of IVD organ culture under proinflammatory conditions to further dissect the role of macrophages in IVD associated immune response. For that, human monocyte-derived macrophages were co-cultured either with bovine caudal IVD punches in the presence of the pro-inflammatory cytokine IL-1ß, or IVD-conditioned medium (CM), to investigate how IVD-produced factors influence macrophage phenotype. After 72 h, metabolic activity, gene expression and cytokine profile of macrophages and IVD cells were measured. Our results show that macrophages and IVDs remain metabolically active in the presence of IL-1ß, significantly upregulate CCR7 gene expression and increase production of IL-6 on macrophages. When treating macrophages with IL-1ß-IVD-CM, CCR7 upregulation follows the same trend, while for IL-6 an opposite effect was observed. On the other hand, macrophages interfere with IVD ECM remodeling, decreasing MMP3 expression and downregulating aggrecan and collagen II gene expression in the presence of IL-1ß. Overall, the co-culture model established in this study can be considered a suitable approach to address the cellular and molecular pathways that regulate macrophage-IVD crosstalk, suggesting that degenerated IVD tissue tends to polarize human macrophages toward a more proinflammatory profile, which seems to aggravate IVD degeneration. This model could be used to improve the knowledge of the mechanisms that link IVD degeneration and the immune response.This work was financed by European Union funds through Bioengineered Therapies for infectious diseases and tissue regeneration (Norte-01-0145-FEDER-000012), Projetos Estruturados de I& D& I - Norte-01-0145-FEDER-000012, Portugal 2020 - FEDER, and through EUROSPINE TRF (2017_05) by the project Disc degeneration-, immune-, and neuro-modulation. The authors also acknowledge FCT – Fundação para a Ciência e a Tecnologia, in the framework of the FCT Investigator Grant of RMG (IF/00638/2014), CC Junior Research contract (DL 57/2016/CP1360/CT0004) and the Ph.D. grant of JF (PD/BI/128357/2017). The authors would like to thank Serviço de Imunohemoterapia of Centro Hospitalar Universitário de São João (CHUSJ), for kindly donating Buffy Coats

Saccadic Direction Errors are Associated with Impulsive Compulsive Behaviours in Parkinson’s Disease Patients

Fifteen individuals with Parkinson’s disease (PD) and impulsive compulsive behaviours (PD+ICB) were compared to 15 PD patients without ICBs (PD-ICB) and 15 healthy controls (HC) on a pro-saccades and an anti-saccades task to assess if ICBs are associated with distinct saccadic abnormalities. PD+ICB made shorter saccades than HC and more direction errors in the anti-saccades task than PD-ICB and HC, suggesting that patients with ICBs have greater difficulty in suppressing automatic saccades towards a given target. Saccadic assessment has the potential to evolve into a marker to guide therapeutic decisions in patients at risk of developing ICBs