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N Vila-Chã,1–4 S Cavaco1,2, A Mendes,1–3 A Gonçalves,1–3 I Moreira,1–3 J Fernandes2,3, J Damásio1,5, LF Azevedo,4,6–7 J Castro-Lopes6,81Department of Neurology, Centro Hospitalar do Porto, Porto, Portugal; 2Laboratory of Neurobiology of Human Behavior, Centro Hospitalar do Porto, Porto, Portugal; 3Unity in Multidisciplinary Research on Biomedicine (UMIB), Abel Salazar Biomedical Sciences Institute, University of Porto, Porto, Portugal; 4Centre for Health Technology and Services Research (CINTESIS), University of Porto, Porto, Portugal; 5Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal; 6National Observatory for Pain – NOPain, Faculty of Medicine, University of Porto, Porto, Portugal; 7Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine, University of Porto, Porto, Portugal; 8Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, PortugalIntroduction: Sleep disturbances and pain are common non-motor symptoms in Parkinson’s disease (PD). This study aimed to explore the association between these two symptoms in a cohort of patients with PD.Materials and methods: The Parkinson’s Disease Sleep Scale (PDSS-2) was used to identify sleep disturbances in a series of 229 PD patients. The identification and characterization of pain was performed by a semi-structured interview and by the application of the Ford classification and the Brief Pain Inventory (BPI). The Unified Parkinson’s Disease Rating Scale-III, Hoehn & Yahr (H&Y), and Schwab and England Independence Scale were used to assess motor symptoms and functional independence in off and on conditions. The Hospital Anxiety and Depression Scale (HADS) and SF-36 were applied to screen for anxiety and depression and to evaluate the quality of life. Non-parametric tests were used for group comparisons and logistic regressions were applied to explore predictors of sleep disturbances.Results: Seventy-five (33%) patients had clinically relevant sleep disturbances (PDSS-2≥18) and 162 patients (71%) reported pain. Of those with pain, 38 (24%) had central parkinsonian pain. PD patients with sleep disturbances experienced more pain and had more severe motor symptoms, lower functional independence, more anxiety and depression symptoms, and worst quality of life. Among patients with pain, central parkinsonian pain was the subtype of pain with the highest odds of sleep disturbances, even when taking into account motor symptoms (H&Y off), motor fluctuations, intensity of pain (BPI), and symptoms of anxiety and depression (HADS).Conclusions: The association between pain and sleep disturbances in PD appears to be dependent on subtype of pain. The close relationship between central parkinsonian pain and sleep disturbances in PD raises the possibility of common pathophysiological mechanisms. A better understanding of the relationship between sleep disturbances and central parkinsonian pain may contribute to the development of new care strategies in PD patients.Keywords: Parkinson’s disease, sleep disturbances, central parkinsonian pain

Background:  The magnetic resonance imaging-guided focused ultrasound (MRgFUS) has emerged as an innovative treatment for patients with medically refractory essential tremor (ET)., Objective:  This retrospective observational study aims to present the results of the first five patients with medically refractory ET who underwent MRgFUS treatment at this pioneering medical unit in Portugal., Methods:  We conducted a retrospective chart review for the first five patients who underwent unilateral MRgFUS thalamotomy of the ventral intermediate (Vim) nucleus to treat medically refractory ET at our medical unit., Results:  The mean patient age was 65.4 (26-84) years, and 60% were male. All patients had a family history of ET. The mean duration of disease was 17.4 years (range 10-24 years), and their dominant hand was the right. According to personal preference, the thalamotomy was performed on the left side in four patients, and on the right side in one. The MRgFUS thalamotomy led to significant improvements in both the clinical rating scale for tremor (CRST) score, by 62%, and the CRST composite score for the treated hand, by 73%. All patients experienced improvements in functionality and quality of life, by 52%. No severe adverse events were observed, and those that did occur during and following the procedure were mild and transient., Conclusion:  The initial results from Portugal's first MRgFUS medical unit indicate promising outcomes, with improvement in quality of life, as well as mild and temporary adverse events These findings contribute to the growing body of literature supporting the efficacy and safety of MRgFUS as a viable treatment option for patients with medication-resistant ET., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Introduction: Neurological involvement in immunoglobulin G4-related disease (IgG4-RD) is increasingly recognized. Its diagnosis can be challenging due to clinical mimics and difficulty in obtaining nervous system biopsies. The aim of this study was to describe a cohort of neurological IgG4-RD patients., Methods: Patients were recruited from a neuroimmunology tertiary center. Clinical, laboratory, neuroimaging and histological data were reviewed., Results: Fifteen patients (60% women), with a median age of 53 years (48.5 - 65.0) were included: 13 (86.7%) classified as possible IgG4-RD, one (6.7%) as probable and one (6.7%) as definitive. The most common neurological phenotypes were meningoencephalitis (26.7%), orbital pseudotumor (13.3%), cranial neuropathies (13.3%), peripheral neuropathy (13.3%), and longitudinally extensive transverse myelitis (LTEM) (13.3%). Median serum IgG4 concentration was 191.5 (145.0 - 212.0) mg/dL. Seven in 14 patients had CSF pleocytosis (50.0%) and oligoclonal bands restricted to the intrathecal compartment, while most cases presented elevated CSF proteins (64.3%). Magnetic resonance imaging abnormalities included white matter lesions in four (26.7%), hypertrophic pachymeningitis in two (13.3%), and LETM in two (13.3%). Two patients had biopsy-proven IgG4-RD in extra-neurological sites., Conclusion: This study highlights the phenotypical variability of the neurological IgG4-RD. Biopsy inaccessibility reinforces the importance of new criteria for the diagnosis of this subset of patients.

Background: A possible genetic contribution of dopamine D3 receptor (DRD3) to cognitive impairment in Parkinson's disease (PD) has yet to be investigated., Objective: To explore the effects of rs6280 (Ser9Gly) genotype on PD patients' cognitive performance and to clarify possible interactions with psychopathology., Methods: Two hundred and fifty-three consecutive PD patients underwent neurological and neuropsychological evaluations, which included: Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale (H&Y), Dementia Rating Scale-2 (DRS-2), and Hospital Anxiety and Depression Scale (HADS). rs6280 polymorphism was genotyped for all PD patients and for 270 ethnically matched healthy volunteers (HC). Non-parametric group comparisons and logistic regressions were used for data analyses., Results: rs6280 genotype did not differ between PD and HC groups. PD patients with rs6280 CC genotype had more impaired cognitive performance (i.e., <1st percentile of demographically adjusted norms) on DRS-2 subscales Initiation/Perseveration and Construction than those with TT genotype. These associations remained statistically significant when other covariates (e.g., demographic features, disease duration, severity of motor symptoms in OFF and ON states, anti-parkinsonian medication, and psychopathology symptoms) were taken into consideration. PD patients with rs6280 TC had less anxiety (i.e., HADS Anxiety≥11) than those with TT (p = 0.012). This association was also independent of other covariates., Conclusions: Study findings suggest that rs6280 CC genotype predisposes to executive dysfunction and visuoconstructional deficits, whereas the heterozygous genotype protects from anxiety in PD. These effects do not appear to be dependent of one another. rs6280 is not a genotypic susceptibility factor for PD.

Background: Handicap is a patient-centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late-stage Parkinson's Disease (PD)., Objective: To characterize the handicap of a broader sample of patients., Methods: A cross-sectional study of 405 PD patients during the MDS-UPDRS Portuguese validation study, using the MDS-UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ-8 and EQ-5D-3L. Handicap was measured using the London Handicap Scale (LHS)., Results: Mean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2-3). Mean LHS was 0.652 (±0.204); "Mobility," "Occupation" and "Physical Independence" were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ-8 did not differentiate age groups. Handicap was significantly correlated with disease duration ( r  = -0.35), nonmotor experiences of daily living (EDL) (MDS-UPDRS-I) ( r  = -0.51), motor EDL (MDS-UPDRS-II) ( r  = -0.69), motor disability (MDS-UPDRS-III) ( r  = -0.49), axial signs of MDS-UPDRS-III ( r  = -0.55), HY ( r  = -0.44), presence of nonmotor symptoms ( r  = -0.51) and PDQ-8 index ( r  = -0.64) (all P  < 0.05). Motor EDL, MDS-UPDRS-III and PDQ-8 independently predicted Handicap (adjusted R 2  = 0.582; P  = 0.007)., Conclusions: The LHS was easily completed by patients and caregivers. Patients were mild-moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived-health status in a broad sample of PD., (© 2023 International Parkinson and Movement Disorder Society.)

Peripheral neuropathy is a common problem in patients with Parkinson's disease. Peripheral neuropathy's prevalence in Parkinson's disease varies between 4.8-55%, compared with 9% in the general population. It remains unclear whether peripheral neuropathy leads to decreased motor performance in Parkinson's disease, resulting in impaired mobility and increased balance deficits. We aimed to determine the prevalence and type of peripheral neuropathy in Parkinson's disease patients and evaluate its functional impact on gait and balance. A cohort of consecutive Parkinson's disease patients assessed by movement disorders specialists based on the UK Brain Bank criteria underwent clinical, neurophysiological (nerve conduction studies and quantitative sensory testing) and neuropathological (intraepidermal nerve fibre density in skin biopsy punches) evaluation to characterize the peripheral neuropathy type and aetiology using a cross-sectional design. Gait and balance were characterized using wearable health-technology in OFF and ON medication states, and the main parameters were extracted using validated algorithms. A total of 99 Parkinson's disease participants with a mean age of 67.2 (±10) years and mean disease duration of 6.5 (±5) years were assessed. Based on a comprehensive clinical, neurophysiological and neuropathological evaluation, we found that 40.4% of Parkinson's disease patients presented peripheral neuropathy, with a predominance of small fibre neuropathy (70% of the group). In the OFF state, the presence of peripheral neuropathy was significantly associated with shorter stride length (P = 0.029), slower gait speed (P = 0.005) and smaller toe-off angles (P = 0.002) during straight walking; significantly slower speed (P = 0.019) and smaller toe-off angles (P = 0.007) were also observed during circular walking. In the ON state, the above effects remained, albeit moderately reduced. With regard to balance, significant differences between Parkinson's disease patients with and without peripheral neuropathy were observed in the OFF medication state during stance with closed eyes on a foam surface. In the ON states, these differences were no longer observable. We showed that peripheral neuropathy is common in Parkinson's disease and influences gait and balance parameters, as measured with mobile health-technology. Our study supports that peripheral neuropathy recognition and directed treatment should be pursued in order to improve gait in Parkinson's disease patients and minimize balance-related disability, targeting individualized medical care., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Intraepidermal nerve fiber density (IENFD) measurements in skin biopsy are performed manually by 1-3 operators. To improve diagnostic accuracy and applicability in clinical practice, we developed an automated method for fast IENFD determination with low operator-dependency. Sixty skin biopsy specimens were stained with the axonal marker PGP9.5 and imaged using a widefield fluorescence microscope. IENFD was first determined manually by 3 independent observers. Subsequently, images were processed in their Z-max projection and the intradermal line was delineated automatically. IENFD was calculated automatically (fluorescent images automated counting [FIAC]) and compared with manual counting on the same fluorescence images (fluorescent images manual counting [FIMC]), and with classical manual counting (CMC) data. A FIMC showed lower variability among observers compared with CMC (interclass correlation [ICC] = 0.996 vs 0.950). FIMC and FIAC showed high reliability (ICC = 0.999). A moderate-to-high (ICC = 0.705) was observed between CMC and FIAC counting. The algorithm process took on average 15 seconds to perform FIAC counting, compared with 10 minutes for FIMC counting. This automated method rapidly and reliably detects small nerve fibers in skin biopsies with clear advantages over the classical manual technique., (© 2021 American Association of Neuropathologists, Inc.)

Accurate assessment of Parkinson's disease (PD) ON and OFF states in the usual environment is essential for tailoring optimal treatments. Wearables facilitate measurements of gait in novel and unsupervised environments; however, differences between unsupervised and in-laboratory measures have been reported in PD. We aimed to investigate whether unsupervised gait speed discriminates medication states and which supervised tests most accurately represent home performance. In-lab gait speeds from different gait tasks were compared to home speeds of 27 PD patients at ON and OFF states using inertial sensors. Daily gait speed distribution was expressed in percentiles and walking bout (WB) length. Gait speeds differentiated ON and OFF states in the lab and the home. When comparing lab with home performance, ON assessments in the lab showed moderate-to-high correlations with faster gait speeds in unsupervised environment ( r = 0.69; p < 0.001), associated with long WB. OFF gait assessments in the lab showed moderate correlation values with slow gait speeds during OFF state at home ( r = 0.56; p = 0.004), associated with short WB. In-lab and daily assessments of gait speed with wearables capture additional integrative aspects of PD, reflecting different aspects of mobility. Unsupervised assessment using wearables adds complementary information to the clinical assessment of motor fluctuations in PD.

Gait speed often referred as the sixth vital sign is the most powerful biomarker of mobility. While a clinical setting allows the estimation of gait speed under controlled conditions that present functional capacity, gait speed in real-life conditions provides the actual performance of the patient. The goal of this study was to investigate objectively under what conditions during daily activities, patients perform as well as or better than in the clinic. To this end, we recruited 27 Parkinson's disease (PD) patients and measured their gait speed by inertial measurement units through several walking tests in the clinic as well as their daily activities at home. By fitting a bimodal Gaussian model to their gait speed distribution, we found that on average, patients had similar modes in the clinic and during daily activities. Furthermore, we observed that the number of medication doses taken throughout the day had a moderate correlation with the difference between clinic and home. Performing a cycle-by-cycle analysis on gait speed during the home assessment, overall only about 3% of the strides had equal or greater gait speeds than the patients' capacity in the clinic. These strides were during long walking bouts (>1 min) and happened before noon, around 26 min after medication intake, reaching their maximum occurrence probability 3 h after Levodopa intake. These results open the possibility of better control of medication intake in PD by considering both functional capacity and continuous monitoring of gait speed during real-life conditions.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a late-onset, multisystem ataxia that remained only clinically defined, until recently, when the discovery of biallelic repeat expansion in the RFC1 gene allowed the genetic link. We describe the first Portuguese familial CANVAS harboring the pathogenic RFC1 expansion. Detail clinical features and course of four affected members are provided. Phenotype characterizations are important as the novel RFC1 mutation is expected to be a major cause of idiopathic late-onset ataxia.

Introduction: The vermiform appendix is a potential site of initiation of Parkinson's disease (PD) pathology. We hypothesized that the appendectomy earlier in life may alter the clinical expression of PD., Objective: To explore the effects of appendectomy prior to onset of PD motor symptoms on patients' symptoms, in particular on cognitive dysfunction., Methods: Two hundred and sixty-two consecutive PD patients were asked about past history of appendectomy and underwent an evaluation, which included the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale (H&Y), Schwab & England Independence Scale (S&E), Dementia Rating Scale-2 (DRS-2), Apathy Evaluation Scale, Hospital Anxiety and Depression Scale, and Brief Smell Identification Test. Motor symptoms were evaluated in OFF and ON states. Non-parametric group comparisons and logistic regressions were used for data analyses., Results: Thirty-one patients (11.8%) had history of appendectomy prior to PD onset. These patients had more severe motor symptoms (UPDRS-III and H&Y) and lower functional independence (S&E) in ON and had higher frequency of cognitive dysfunction (DRS-2 Initiation/Perseveration, Conceptualization, and Memory subscales) (p < 0.05). The association between history of appendectomy and cognitive dysfunction was evident only in patients with late onset PD (≥ 55 years) and with disease duration ≤ 5 years. History of appendectomy remained statistically associated with impairment on DRS-2 Conceptualization and Memory subscales, when demographic and clinical variables were considered., Conclusion: History of appendectomy appears to alter the clinical expression of late onset PD, with early cognitive impairment, more severe motor symptoms in ON, and poorer functional independence under anti-parkinsonian medication.

The occurrence of peripheral neuropathy (PNP) is often observed in Parkinson's disease (PD) patients with a prevalence up to 55%, leading to more prominent functional deficits. Motor assessment with mobile health technologies allows high sensitivity and accuracy and is widely adopted in PD, but scarcely used for PNP assessments. This review provides a comprehensive overview of the methodologies and the most relevant features to investigate PNP and PD motor deficits with wearables. Because of the lack of studies investigating motor impairments in this specific subset of PNP-PD patients, Pubmed, Scopus, and Web of Science electronic databases were used to summarize the state of the art on PNP motor assessment with wearable technology and compare it with the existing evidence on PD. A total of 24 papers on PNP and 13 on PD were selected for data extraction: The main characteristics were described, highlighting major findings, clinical applications, and the most relevant features. The information from both groups (PNP and PD) was merged for defining future directions for the assessment of PNP-PD patients with wearable technology. We established suggestions on the assessment protocol aiming at accurate patient monitoring, targeting personalized treatments and strategies to prevent falls and to investigate PD and PNP motor characteristics.

Background: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany)., Methods: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters., Discussion: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.

Background: Pain in Parkinson's disease (PD) is a common and heterogeneous non-motor symptom. Although the characteristics and predictors of pain in general and of central pain in particular are still largely unknown., Methods: A semi-structured interview, the Brief Pain Inventory and the Pain Disability Index were used to identify and characterize pain in a consecutive series of 292 PD patients. Unified PD Rating Scale-III, Hoehn & Yahr, Schwab and England Independence Scale and Freezing of Gait Questionnaire were applied to assess motor symptoms and functional independence in off and on conditions. Hospital Anxiety and Depression Scale and Questionnaire of Impulsive-Compulsive Control Disorders were used to screen for anxiety, depression and impulse control disorders., Results: Two hundred and twelve patients (73%) reported pain, which was classified as: musculoskeletal (63%), dystonia-related (27%), central parkinsonian (22%) and/or radicular or neuropathic (9%). Patients with pain had more comorbidities and more severe motor symptoms. Patients with central parkinsonian pain were significantly younger, had earlier disease onset, fewer comorbidities, greater non-axial motor symptom severity in on, more pain-related disability and more relief of pain with antiparkinsonian medication than patients with non-central parkinsonian pain., Conclusions: PD patients with central parkinsonian pain have some distinctive demographic and clinical features, including lower levodopa responsiveness of motor appendicular/limb symptoms to levodopa, associated with greater responsiveness of pain symptoms to these same medications. These findings suggest the need for a more integrated approach to motor and non-motor symptoms in these patients' clinical care., Significance: In a consecutive series of 292 patients with PD, almost three quarters of patients with PD reported pain. The study results revealed that pain was related to more severe motor symptoms, anxiety symptoms and comorbidities. Among patients with pain, those with central parkinsonian subtype had distinct demographic and clinical features, including lower levodopa responsiveness for non-axial motor symptoms and greater responsiveness of pain to antiparkinsonian treatment., (© 2019 European Pain Federation - EFIC®.)

The expansion in the C9orf72 gene has been recently reported as a genetic cause of Huntington's disease (HD) phenocopies. We aim to assess the frequency of the C9orf72 gene expansion in a Portuguese HD phenocopies cohort. Twenty HD phenotype-like patients without diagnosis were identified in our institutional database. C9orf72 gene expansion was detected using repeat-primed PCR. Clinical files were reviewed to characterize the phenotype of expansion-positive cases. One patient (5%) was positive for the C9orf72 expansion. A second patient presented 27 repeats-within the intermediate size interval. Both had familial neuropsychiatric disease characterized by diverse movement disorders, dementia, and psychiatric dysfunction that was distinct in severity and clinical expression. C9orf72 disease is clinically heterogeneous and without evident imaging markers. The definition of the role of intermediate alleles and of the pathological threshold for C9orf72 repeat expansions may have diagnostic implications.

Background: The rate of Parkinson's disease (PD) progression varies widely between patients. Current knowledge does not allow to accurately predict the evolution of symptoms in a given individual over time., Objectives: To develop regression-based models of PD progression and to explore its predictive value in a three-year follow-up., Methods: At baseline, 300 consecutive PD patients were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) - subscales II and III, Hoehn & Yahr (H&Y) and Schwab and England Independence Scale (S&E); and the Freezing of Gait Questionnaire (FOG-Q). UPDRS-III and H&Y were applied in OFF and ON medication conditions. An axial index was derived from the UPDRS-III. Based on multiple linear regression coefficients, algorithms were developed to adjust test scores to the characteristics of each individual. Sixty-eight patients were reevaluated three years later., Results: In the construction of the models, disease duration, age ≥70, age at disease onset ≥55, tremor as the first symptom alone, and medication description explained between 35% (UPDRS-III in ON) and 57% (axial index in ON) of the variance of test scores. The predictive r2 of the models in a 10-fold cross-validation ranged between 33% (UPDRS-III in ON) and 55% (axial index in ON and S&E in OFF). All measures, except UPDRS-III OFF, H&Y ON, and S&E ON, had moderate/good absolute agreement (intraclass correlation coefficient between 0.60 and 0.72) between baseline and follow-up., Conclusions: A cross-sectional assessment of a PD population allowed the development of models of disease progression, whose predictive value was validated on a three-year longitudinal study.

Introduction: Parkinson's disease is associated with high hospital mortality. Male gender, late age at onset, higher disability and the coexistence of cognitive impairment or depression have been suggested to be risk factors of death. Pneumonia and cardiovascular diseases are the leading causes of death., Objective: To characterize the mortality (causes of hospital admission and death) of Parkinson's disease patients in a tertiary hospital, as well as demographic and clinical characteristics., Material and Methods: Identification of hospital admissions of Parkinson's disease patients that resulted in inpatient death between 2008 and 2014. Retrospective review of medical files and inclusion of patients with disease clinically confirmed by a neurologist. Assessment of causes of death and demographic and clinical characteristics of patients., Results: 1525 hospital admissions of Parkinson's disease patients were identified, of which 150 resulted in death. Of these, 52 patients met the inclusion criteria. Mean age at onset of Parkinson's disease symptoms was 66.8 years (± 8.7) and mean duration of disease was 12.5 years (± 7.9). Sixty-five percent of patients were in stages 4-5 of the Hoehn and Yahr scale. Thirty-three patients (63%) had dementia and eleven (21%) had depression. Infections were the leading cause of death (respiratory in 63% of cases)., Discussion: Similarly to literature, pneumonia was the leading cause of hospital death and most patients presented advanced disease stage and dementia. Contrarily to other studies, life expectancy was not reduced and cardiovascular diseases and trauma were not causes of death in our population., Conclusions: This is the first Portuguese mortality study in Parkinson's disease. Pneumonia is the leading cause of death. Advanced disease stage and dementia were common features in these patients.

Background: Alpha-synuclein (α-Syn) is particularly abundant in the vermiform appendix, which makes this structure an anatomical candidate for the initiation of Parkinson's disease (PD) pathology. We hypothesized that history of appendectomy might affect PD clinical onset., Methods: A total of 295 PD patients enrolled in a comprehensive observational study were asked about past history of appendectomy. Cox's regression, with a time-dependent covariate, explored the effects of appendectomy on age at PD onset., Results: Thirty-four patients (11.5%) had appendectomy before PD onset. There was no significant effect of appendectomy on age at PD onset for the entire cohort (P = 0.153). However, among patients with late onset (≥55 years), we found evidence that those with past appendectomy had more years of life without PD symptoms than patients without appendectomy (P = 0.040). No association was found for the young-onset group (P = 0.663)., Conclusions: An apparent relationship was observed between appendectomy and PD onset in the late PD cohort., (© 2015 International Parkinson and Movement Disorder Society.)

Introduction: A possible association between olfactory dysfunction and Parkinson's disease (PD) severity has been a topic of contention for the past 40 years. Conflicting reports may be partially explained by procedural differences in olfactory assessment and motor symptom evaluation., Methods: One hundred and sixty-six nondemented PD patients performed the Brief-Smell Identification Test and test scores below the estimated 20th percentile as a function of sex, age, and education (i.e., 80% specificity) were considered demographically abnormal. Patients underwent motor examination after 12 h without antiparkinsonian medication., Results: Eighty-two percent of PD patients had abnormal olfaction. Abnormal performance on the Brief-Smell Identification Test was associated with higher disease severity (i.e., Hoehn and Yahr, Unified Parkinson's Disease Rating Scale-III, Freezing of Gait questionnaire, and levodopa equivalent dose), even when disease duration was taken into account., Conclusions: Abnormal olfaction in PD is associated with increased severity and faster disease progression.