Peripheral neuropathy in Parkinson's disease: prevalence and functional impact on gait and balance.

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.

Past appendectomy may be related to early cognitive dysfunction in Parkinson's disease.

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.

Spasmodic cough preceding CANVAS phenotype in a family with biallelic repeat expansions in RFC1.

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.

Comparison of Laboratory and Daily-Life Gait Speed Assessment during ON and OFF States in Parkinson's Disease.

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.

Wearable Health Technology to Quantify the Functional Impact of Peripheral Neuropathy on Mobility in Parkinson's Disease: A Systematic Review.

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.

Clinical features of hypertrophic pachymeningitis in a center survey.

BACKGROUND: Hypertrophic pachymeningitis (HP) is characterized by cranial and/or spinal thickening of the dura mater with or without associated inflammation. Neuroimaging studies reveal dura mater thickening and focal or diffuse contrast enhancement. It is described in association with trauma, infections, tumors, autoimmune/inflammatory diseases, and cerebrospinal fluid hypotension syndrome, with some cases remaining idiopathic. METHODS: A retrospective study was conducted with patients' identification through a key terms search within MRI reports in the period of July 2008 to September 2015. Clinical files, MRI, laboratory, and pathology data were reviewed. RESULTS: Fifty-three patients were identified and 20 were excluded because they did not meet the inclusion criteria. Of the 33 included, 19 were female, with a mean age at symptoms onset of 51.2 ± 17.6 years. The most common presenting symptoms were headache and cranial nerves palsy, followed by seizures, delirium, lumbar pain, cognitive decline, motor deficit, and language impairment. In 17 patients, a neoplastic etiology was identified; in eight, inflammatory/autoimmune; in six, infectious; and two were classified as idiopathic. Of the eight patients with inflammatory/autoimmune etiology, four had possible IgG4-related disease (IgG4-RD) and the remaining had granulomatosis with polyangiitis, sarcoidosis, rheumatoid arthritis, and Tolosa-Hunt syndrome. Treatment was directed according to the underlying etiology. DISCUSSION: In the described series, a female predominance was identified, with symptoms' onset in the 5th decade. Although headache was the most common symptom, clinical presentation was varied, emphasizing the role of MRI in HP diagnosis. The underlying etiologies were diverse, with only a few cases remaining idiopathic, also reflecting the contribution of the recently described IgG4-RD.

Clinical spectrum of C9orf72 expansion in a cohort of Huntington's disease phenocopies.

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.

Appendectomy may delay Parkinson's disease Onset.

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.

Initial outcomes and safety of MR guided focused ultrasound (MRgFUS) thalamotomy for essential tremor of the first FUS Medical Unit in Portugal.

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.

ANTECEDENTES: A talomotomia por ultrassons focados - guiada por imagem de ressonância magnética (MRgFUS) surgiu recentemente como um tratamento inovador para pacientes com tremor essencial (TE) refratário ao tratamento médico. OBJETIVO: Este estudo observacional retrospectivo tem como objetivo apresentar os resultados dos primeiros cinco pacientes com TE refratário à medicação submetidos ao tratamento com MRgFUS numa unidade médica pioneira em Portugal. MéTODOS: Realizamos uma revisão retrospectiva dos dados clínicos dos cinco primeiros pacientes submetidos a talamotomia MRgFUS unilateral do núcleo ventral intermédio (Vim) para tratamento do TE medicamente refratário em nossa unidade médica. RESULTADOS: A idade média dos pacientes era de 65,4 (26­84) anos, e 60% eram do sexo masculino. Todos os pacientes tinham história familiar de TE. A duração média da doença foi de 17,4 anos, e todos eram destros. De acordo com a preferência individual, em 4 pacientes, a talamotomia foi realizada no lado esquerdo, e em um, no lado direito. A talamotomia por MRgFUS levou a melhorias significativas tanto na pontuação da escala de classificação clínica para tremor (CRST), de 62%, e na pontuação composta da CRST para a mão tratada, de 73%. Todos os pacientes apresentaram melhorias na funcionalidade e na qualidade de vida, de 52%. Não foram observados efeitos adversos graves e os que ocorreram durante e após o procedimento foram ligeiros e transitórios. CONCLUSãO: Os resultados iniciais da primeira unidade médica MRgFUS de Portugal indicam melhorias na qualidade de vida dos pacientes, com efeitos adversos ligeiros e transitórios. Estes dados reforçam a evidência crescente sobre a eficácia e segurança da talamotomia por MRgFUS como opção viável para pacientes com TE resistente à medicação.

DRD3 Predicts Cognitive Impairment and Anxiety in Parkinson's Disease: Susceptibility and Protective Effects.

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.

Neurological Involvement in a Portuguese Cohort of IgG4-Related Disease.

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.

Handicap as a Measure of Perceived-Health Status in Parkinson's Disease.

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.

Gait speed in clinical and daily living assessments in Parkinson's disease patients: performance versus capacity.

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.

Advantages of an Automated Method Compared With Manual Methods for the Quantification of Intraepidermal Nerve Fiber in Skin Biopsy.

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.

Initial outcomes and safety of MR guided focused ultrasound (MRgFUS) thalamotomy for essential tremor of the first FUS Medical Unit in Portugal / Resultados iniciais e segurança da talamotomia por ultrassons focalizados guiados por RM (MrgFUS) no tremor essencial da primeira Unidade Médica de FUS em Portugal

Abstract 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.

Resumo Antecedentes A talomotomia por ultrassons focados - guiada por imagem de ressonância magnética (MRgFUS) surgiu recentemente como um tratamento inovador para pacientes com tremor essencial (TE) refratário ao tratamento médico. Objetivo Este estudo observacional retrospectivo tem como objetivo apresentar os resultados dos primeiros cinco pacientes com TE refratário à medicação submetidos ao tratamento com MRgFUS numa unidade médica pioneira em Portugal. Métodos Realizamos uma revisão retrospectiva dos dados clínicos dos cinco primeiros pacientes submetidos a talamotomia MRgFUS unilateral do núcleo ventral intermédio (Vim) para tratamento do TE medicamente refratário em nossa unidade médica. Resultados A idade média dos pacientes era de 65,4 (26-84) anos, e 60% eram do sexo masculino. Todos os pacientes tinham história familiar de TE. A duração média da doença foi de 17,4 anos, e todos eram destros. De acordo com a preferência individual, em 4 pacientes, a talamotomia foi realizada no lado esquerdo, e em um, no lado direito. A talamotomia por MRgFUS levou a melhorias significativas tanto na pontuação da escala de classificação clínica para tremor (CRST), de 62%, e na pontuação composta da CRST para a mão tratada, de 73%. Todos os pacientes apresentaram melhorias na funcionalidade e na qualidade de vida, de 52%. Não foram observados efeitos adversos graves e os que ocorreram durante e após o procedimento foram ligeiros e transitórios. Conclusão Os resultados iniciais da primeira unidade médica MRgFUS de Portugal indicam melhorias na qualidade de vida dos pacientes, com efeitos adversos ligeiros e transitórios. Estes dados reforçam a evidência crescente sobre a eficácia e segurança da talamotomia por MRgFUS como opção viável para pacientes com TE resistente à medicação.

Unveiling the relationship between central parkinsonian pain and motor symptoms in Parkinson's disease.

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.

[Hospital Mortality in Parkinson's Disease: Retrospective Analysis in a Portuguese Tertiary Centre]. / Mortalidade Hospitalar na Doença de Parkinson: Análise Retrospetiva num Hospital Terciário Português.

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.

Introdução: A doença de Parkinson está associada a elevada mortalidade hospitalar. O sexo masculino, o início tardio da doença, o grau de incapacidade e a coexistência de deterioração cognitiva ou de depressão têm sido apontados como fatores de risco. A pneumonia e as doenças cardiovasculares são as principais causas de morte. Objetivo: Explorar a mortalidade hospitalar (motivo de internamento e de óbito) dos doentes com doença de Parkinson num hospital terciário, assim como as características demográficas e clínicas. Material e Métodos: Identificação das admissões hospitalares dos doentes com o diagnóstico de doença de Parkinson entre 2008 e 2014 e seleção dos doentes falecidos. Revisão retrospetiva dos processos clínicos e inclusão dos doentes com doença confirmada clinicamente por um neurologista. Avaliação das causas de óbito, características demográficas e clínicas. Resultados: Identificámos 1 525 admissões hospitalares de doentes com diagnóstico de doença de Parkinson, das quais 150 resultaram em óbito. Destes, 52 cumpriam critérios de inclusão. A idade média do início dos sintomas de doença foi 66,8 anos (± 8,7) e a duração média da doença foi 12,5 anos (± 7,9). Sessenta e cinco por cento dos doentes encontravam-se no estádio 4-5 na escala de Hoehn e Yahr. Trinta e três doentes (63%) apresentavam demência e onze depressão. As infeções foram a principal causa de morte (respiratória em 63% dos casos). Discussão: Ã semelhança da literatura, a pneumonia foi a principal causa de morte hospitalar e a maioria dos doentes apresentava estádio avançado de doença e demência. Contrastando com outros estudos, não se verificou diminuição da esperança média de vida e as doenças cardiovasculares e o traumatismo não foram causas de morte na nossa população. Conclusões: Apresentamos o primeiro estudo português de mortalidade na doença de Parkinson. A pneumonia é a principal causa de morte hospitalar. O estádio avançado de doença e a demência foram características comuns nestes doentes.

Statistical Models of Parkinson's Disease Progression: Predictive Validity in a 3-Year Follow-up.

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.