Vanderci Borges

Gender-related differences in the burden of non-motor symptoms in Parkinson’s disease

Differences in the expression of non-motor symptoms (NMS) by Parkinson’s disease (PD) patients may have important implications for their management and prognosis. Gender is a basic epidemiological variable that could influence such expression. The present study evaluated the prevalence and severity of NMS by gender in an international sample of 951 PD patients, 62.63% males, using the non-motor symptoms scale (NMSS). Assessments for motor impairment and complications, global severity, and health state were also applied. All disease stages were included. No significant gender differences were found for demographic and clinical characteristics. For the entire sample, the most prevalent symptoms were Nocturia (64.88%) and Fatigue (62.78%) and the most prevalent affected domains were Sleep/Fatigue (84.02%) and Miscellaneous (82.44%). Fatigue, feelings of nervousness, feelings of sadness, constipation, restless legs, and pain were more common and severe in women. On the contrary, daytime sleepiness, dribbling saliva, interest in sex, and problems having sex were more prevalent and severe in men. Regarding the NMSS domains, Mood/Apathy and Miscellaneous problems (pain, loss of taste or smell, weight change, and excessive sweating) were predominantly affected in women and Sexual dysfunction in men. No other significant differences by gender were observed. To conclude, in this study significant differences between men and women in prevalence and severity of fatigue, mood, sexual and digestive problems, pain, restless legs, and daytime sleepiness were found. Gender-related patterns of NMS involvement may be relevant for clinical trials in PD.

Quality of life scale in parkinson's disease PDQ-39 - (Brazilian Portuguese version) to assess patients with and without levodopa motor fluctuation

A qualidade de vida (QdV) e um item importante para se mensurar o sucesso do tratamento na doenca de Parkinson (DP). O objetivo deste estudo foi o de avaliar a utilidade do questionario sobre a doenca de Parkinson - PDQ-39 (versao em lingua portuguesa falada no Brasil) para mensurar a QdV dos pacientes parkinsonianos com e sem flutuacao motora. Nos avaliamos 56 pacientes com DP com tempo medio da doenca de 7,4 anos, e destes 41 (73,3%) apresentavam flutuacao motora. A PDQ-39 tem oito dominios que variam de 0 a 100 e quanto maior o escore pior a QdV. A comparacao dos grupos de pacientes com e sem flutuacao motora mostrou que os dominios: mobilidade, atividades de vida diaria, comunicacao e desconforto corporal tinham escores maiores nos flutuadores. Quanto maiores os estagios de Hoehn e Yahr (HY) da doenca, maiores os escores da PDQ-39. Pacientes com mais de 5 anos de evolucao da doenca mostraram escores piores da PDQ39 apenas nos itens atividades da vida diaria e comunicacao se comparados a pacientes com 5 anos ou menos de doenca. A PDQ-39 e um instrumento capaz de detectar declinio da QdV de pacientes com DP e a presenca de flutuacao motora e um preditor para reducao na QdV.Quality of life (QoL) is an important treatment outcome indicator in Parkinsons disease (PD). The aim of this study is to assess the usefulness of the Parkinsons disease questionnaire--PDQ-39 (Brazilian Portuguese Version) in measuring QoL of PD patients with or without motor fluctuations. Fifty-six PD patients with mean disease duration of 7.4 years were assessed and 41 of them (73.3%) had motor fluctuations. The PDQ-39 has eight dimensions ranging from 0 to 100; being the higher the score, the worse the QoL. Comparing groups with and without motor fluctuations showed that the dimensions mobility, activities of daily living (ADL), communication and bodily discomfort scored higher in the fluctuating group. There was a tendency to see that the higher the Hoehn and Yahr (HY) scale stages, the higher the PDQ-39 scores. Patients suffering from the disease for more than five years had worse PDQ-39 scores only in the items ADL and communication, when compared with those with the disease for < 5 years. The PDQ-39 is an instrument that detects decrease in QoL of PD patients and the presence of motor fluctuations predicts QoL reduction.

Effect of riluzole on dyskinesia and duration of the on state in Parkinson disease patients: a double-blind, placebo-controlled pilot study.

The objective of this study was to evaluate the effect of riluzole on dyskinesia and the duration of the ON state in patients with Parkinson disease (PD). The authors studied 16 PD patients with levodopa-induced dyskinesia. All patients initially received an apomorphine dose intended to induce the motor function benefit (ON state) generally accompanied by dyskinesia. They evaluated the patients during the OFF and ON states using the UPDRS-III, UPDRS-IV, and Larsen scales, and measured the duration of the ON state. Patients were randomly assigned to receive either riluzole (50 mg bid) or placebo for 7 consecutive days (8 patients in each group). The authors did not interrupt previously prescribed medication. Following the 7-day period, they carried out similar evaluation procedures before and after another apomorphine challenge. Mean UPDRS-IV scores were 6.1 points and 6.0 points before and after riluzole therapy respectively. For the placebo group, the scores were 6.9 points and 6.6 points for the initial and final evaluations respectively. Larsen scale had mean scores of 9.2 points and 9.9 points for the pre- and postriluzole periods, and 10.2 points and 9.6 points for pre- and post-placebo evaluations respectively. The ON state was 33.5% lengthier after 7 days of riluzole and 28.0% lengthier after placebo. They could not find any statistical differences between the 2 groups. Short-term riluzole administration in PD patients was not able to reduce apomorphine-induced dyskinesia but could extend the ON state duration, although this did not reach statistical significance.

Higher dopamine transporter density in Parkinson’s disease patients with depression

RationaleDepression is a frequent non-motor symptom in Parkinson’s disease (PD) with increasing rates with the progression of the disease. Molecular imaging studies have shown a reduction of dopamine transporter (DAT) density in depressed PD patients (dPD); however, DAT role in the pathophysiology of PD depression is not clear since clinical matching was inappropriate and DAT reduction could be attributed to PD severity.ObjectivesTo further examine the role of DAT in PD depression, this study compared thoroughly matched depressed vs. non-depressed PD patients (ndPD).Materials and methodsTwenty PD patients (n = 10 ndPD; n = 10 dPD) matched for age and disease severity were submitted to brain SPECT imaging with [99mTc]-TRODAT-1, a DAT radioligand. DAT-binding potential was calculated using regions of interest bilaterally drawn in the striatum, caudate, and putamen. Depression was defined according to Beck Depression Inventory (BDI; cut-off >18).ResultsMean BDI scores were higher in dPD (25.0 ± 5.6) than in ndPD patients (8.0 ± 1.9, p < 0.0001). DAT density was greater on dPD especially in the left caudate (dPD 0.87 ± 0.19 vs. ndDP 0.69 ± 0.18, p = 0.02) and right putamen (dPD 0.37 ± 0.07 vs. ndPD 0.28 ± 0.13, p = 0.03) than in ndPD patients.ConclusionOur results suggest that in vivo DAT density is increased in dPD patients as compared to ndPD, suggesting that DAT is implicated in the pathophysiology of PD depression.

Genetic and environmental findings in early‐onset Parkinson's disease Brazilian patients

Parkinsons disease (PD) etiology has been attributed both to genetic and environmental factors. In this study, we investigated Brazilian early‐onset PD (EOPD) patients for mutations in PARK2 and PARK8, exposure to environmental factors and possible correlations between PARK2 polymorphisms, environmental exposure, and disease age of onset. We enrolled 72 EOPD index patients and 81 healthy volunteers. Both groups were investigated for environmental exposure. EOPD patients were screened for PARK2 and PARK8 mutations. PARK2 coding polymorphisms Ser167Asn and Val380Leu were investigated in both groups. Mutations were present in 18% of the patients and in 32% of those with a positive family history. PARK2 mutations represented 12.5% and PARK8 mutations accounted for 5.5% of the mutations. A novel PARK2 mutation (D53X) was identified in 2 patients. A positive correlation was found between EOPD and well water drinking. In patients exposed to well water, a later age of onset was observed for those who carried at least one PARK2 380Leu allele. PARK2 mutations have an important role in EOPD Brazilian patients and PARK8 might be the second most important disease causing gene in this group. Well water drinking exposure represents a risk factor for EOPD and the PARK2 coding polymorphism Val380Leu might be interacting with environmental factors acting as a disease modifier.

Screening of Brazilian families with primary dystonia reveals a novel THAP1 mutation and a de novo TOR1A GAG deletion.

The TOR1A and THAP1 genes were screened for mutations in a cohort of 21 Brazilian patients with Primary torsion dystonia (PTD). We identified a de novo delGAG mutation in the TOR1A gene in a patient with a typical DYT1 phenotype and a novel c.1A > G (p.Met1?) mutation in THAP1 in a patient with early onset generalized dystonia with speech involvement. Mutations in these two known PTD genes, TOR1A and THAP1, are responsible for about 10% of the PTD cases in our Brazilian cohort suggesting genetic heterogeneity and supporting the role of other genes in PTD.

Tremor postural e distonia: aspectos clínicos e considerações fisiopatológicas

The coexistence of tremor and dystonia is usually seen but there is not a satisfactory explanation for it. Some consider that essential tremor (ET) and idiopathic dystonia (ID) may be genetically linked. To clarify this relationship we evaluated the frequency of postural hand tremor in ID and symptomatic dystonia (SD) patients. We studied the records of patients with dystonia seen in our Movement Disorders Unit. ID was considered when there was no other neurological abnormality in the examination aside from dystonia, normal laboratorial tests and neuroimaging related to dystonia, and a negative past history for any known cause for it, except for genetic predisposition. We analyzed the clinical characteristics of dystonia and the occurrence of postural tremor. We collected 185 patients, being 120 with ID and 65 with SD. Tremor was seen in 27 (22.5%) of ID and 14 (21.5%) of SD. Tremor was present in either focal, segmental or generalized dystonia in both ID and SD. Family history for ET was absent in all patients. The similar frequency of tremor in ID and SD patients suggests that the pathophysiologic derangement resulting in dystonia can favor the development of tremor.A presenca de tremor e distonia de torcao no mesmo paciente e frequente mas nao ha uma explicacao satisfatoria para isso. Suspeita-se que haja uma associacao da distonia idiopatica (DI) com o tremor essencial (TE). O objetivo deste estudo e analisar a frequencia de tremor postural das maos em pacientes com DI e distonia sintomatica (DS). Foram estudados os prontuarios de 185 pacientes com o diagnostico sindromico de distonia atendidos no Setor de Investigacao em Molestias Extrapiramidais da Escola Paulista de Medicina. DI foi diagnosticada quando nao havia anormalidade no exame neurologico alem da distonia e havia exames laboratoriais e de neuroimagem, relacionados a distonia, normais e historia pregressa negativa para fatores causais de distonia. Foram analisadas as caracteristicas clinicas da distonia e a presenca de tremor postural nas maos. Havia 185 pacientes, 120 com DI e 65 com DS. Tremor postural das maos ocorreu em 27 (22,5%) das DI e 14 (21,5%) das DS. Tremor esteve presente nos quadros focais, segmentares e generalizados e tambem nos diversos tipos clinicos de DI e DS em proporcoes semelhantes. Historia familiar de TE estava ausente em todos os casos com tremor. A presenca de tremor postural das maos em pacientes com DI e DS pode sugerir que a desorganizacao fisiopatologica que produz a distonia pode favorecer o aparecimento do tremor.

Depression in Parkinson's disease: clinical-epidemiological correlates and comparison with a controlled group of non-parkinsonian geriatric patients

OBJECTIVE To evaluate and compare the frequency and severity of major depression in patients with Parkinsons disease and in individuals older than 60 years without neurological, rheumatological and/or oncological comorbidities. METHOD We studied 50 patients with Parkinsons disease older than 60 years and 50 geriatric patients. Subjects with scores of Mini Mental State Examination indicating cognitive impairment were excluded. We used Diagnostic Statistical Manual of Mental Diseases-IV criteria to diagnose major depression and the Hamilton Depression Scale and the Beck Depression Inventory to rate it. The Unified Parkinsons Disease Rating Scale part 3 and the Hoehn and Yahr Scale were used to evaluate the motor severity of Parkinsons disease. RESULTS Major depression was found in 42% of Parkinsons disease patients and in 10% of the geriatric patients (p < 0.001). The scores of the Hamilton Depression Scale and the Beck Depression Inventory were higher in Parkinsons disease patients (p < 0.001). Depressed Parkinsons disease patients had longer duration of Parkinsons disease (p = 0.020) and higher scores on the Unified Parkinsons Disease Rating Scale part 3 (p = 0.029) and the Yahr Scale (p = 0.027). CONCLUSIONS The frequency (42%) and severity of major depression were higher in Parkinsons disease patients. Longer duration of Parkinsons disease, higher scores on the Unified Parkinsons Disease Rating Scale part 3 and the Hoehn and Yahr Scale were significantly associated with major depression.

Bilateral hemifacial spasm and trigeminal neuralgia : A unique form of painful tic convulsif

alleviated by lightly stroking his inguinal and inframammary areas, which we interpreted as a sensory trick. He reports occasional paresthesias but denies any weakness or morning paralysis. The cramps cause mild dysphagia and shortness of breath. He denies any orthopnea, diplopia, dysarthria, or upper extremity or facial involvement. He has tried muscle relaxants in the past without relief. There is no family history of neuromuscular disorders. He has had diabetes for the past 1.5 years. He has not taken any medications besides metformin. He does not drink alcohol. Mental status, cranial nerves, sensation, posture, and gait were normal. There were no signs of ocular myotonia. Motor examination of neck and extremities were 5/5 with normal tone. There were no signs of fasciculations, atrophy, muscle spasms, or percussion myotonia. Deep tendon reflexes were mildly brisk diffusely, with hyporeflexic ankle jerks and downgoing toes. CPK was normal and anti-GAD antibodies were absent. Electromyography (EMG) of the right rectus abdominis, superior oblique, and external intercostals demonstrated normal motor units without any denervation potentials, myotonic discharges, or neuromyotonia. Applying ice and abdominal exercises did not provoke any abnormalities. Interestingly, motor unit recruitment was present during active (but not passive) stretching of abdominal muscles by trunk extension, suggesting co-contraction of axial muscles, supporting the diagnosis of dystonia. We prescribed clonazepam as needed, to which his symptoms had responded. To our knowledge, this is the first reported case of occupational dystonia involving the truncal muscles, and that in a bricklayer. The deliberate strong, repeated contraction of abdominal muscles against resistance while bricklaying seems to have led to the dystonia. The EMG provided evidence of co-contraction of abdominal and axial muscles during back extension. Isolated truncal involvement has been described in tardive dystonia1 or idiopathic primary truncal dystonia.2 Botulinum toxin is the treatment of choice for writer’s cramp and other occupational dystonias3; however, due to the widespread involvement, we had initially chosen an oral muscle relaxant.

Clinical features of dystonia in atypical parkinsonism

BACKGROUND The association between Dystonia and Parkinsons disease (PD) has been well described especially for foot and hand dystonia. There is however few data on dystonic postures in patients with atypical parkinsonism. OBJECTIVE To evaluate the frequency and pattern of dystonia in a group of patients with atypical parkinsonism (multiple system atrophy - MSA, progressive supranuclear palsy - PSP, and corticobasal degeneration - CBD) and to investigate whether dystonia could be the first presenting symptom at disease onset in those patients. METHOD A total of 38 medical charts were reviewed (n=23/MSA group; n=7/CBD group; n=8/PSP group) and data values were described as means/standard deviations. The variables evaluated were sex, age at onset, disease duration, first symptom, clinical features of dystonia and other neurological signs, response to levodopatherapy, Hoehn &Yahr -scale >3 after three years of disease, and magnetic resonance imaging findings. RESULTS The overall frequency of dystonia in our sample was 50% with 30.4% (n=7) in the MSA group, 62.5% (n=5) in the PSP group, and 100% (n=8) in the CBD group. In none of these patients, dystonia was the first complaint. Several types of dystonia were found: camptocormia, retrocollis, anterocollis, blepharoespasm, oromandibular, and foot/hand dystonia. CONCLUSION In our series, dystonia was a common feature in atypical parkinsonism (overall frequency of 50%) and it was part of the natural history although not the first symptom at disease onset. Neuroimaging abnormalities are not necessarily related to focal dystonia, and levodopa therapy did not influence the pattern of dystonia in our group of patients.INTRODUCAO: A associacao de distonia e doenca de Parkinson (DP) ja foi bem estabelecida, principalmente para distonia focal em pe ou mao. Entretanto, ha poucos dados quanto a distonia em pacientes com parkinsonismo atipico. OBJETIVO: Avaliar a frequencia e o padrao da distonia em um grupo de pacientes com parkisnonismo atipico (atrofia de multiplos sistemas - AMS; paralisia supranuclear progressiva - PSP; degeneracao corticobasal - DCB) e investigar se a distonia pode ser a manifestacao inicial neste grupo. METODO: Um total de 38 prontuarios medicos foi revisado (n=23/grupo AMS; n=8/grupo PSP; n=7/grupo PSP) e os dados foram apresentados em medias/desvios padroes. As variaveis avaliadas foram: sexo, idade de inicio, duracao da doenca, primeiro sintoma, caracteristicas clinicas da distonia e outros sinais neurologicos, resposta ao tratamento com levodopa, escala de Hoehn & Yahr >3 em 3 anos de doenca, e achados de ressonância magnetica. RESULTADOS: A frequencia total de distonia em nosso grupo foi 50%, sendo 30,4% (n=7) no grupo AMS, 62.5% (n=5) no grupo PSP e 100% (n=8) no grupo DCB. Em nenhum dos pacientes, distonia foi o primeiro sintoma. Varias apresentacoes de distonia foram observadas: camptocormia, anterocolis, retrocolis, distonia oromandibular, em pe e mao. CONCLUSAO: Em nossa serie, distonia foi uma caracteristica comum em pacientes com parkinsonismo atipico (frequencia de 50%) e fez parte da historia natural em todos os grupos, embora nao tenha sido o sintoma inicial em nenhum deles. Anormalidades no exame de neuroimagem nao necessariamente estao relacionadas a distonia focal, e o tratamento com levodopa nao influenciou o padrao da distonia em nosso grupo de pacientes.