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BACKGROUND: Patients with Multiple System Atrophy (MSA) frequently report non-motor symptoms, and several research groups have highlighted this. OBJECTIVE: We systematically searched for and reviewed papers assessing prevalence of non-motor symptoms (NMS) in MSA patients as reported in the scientific literature. METHODS: We performed a systematic review of studies of subjects with MSA (involving > 10 patients) who were assessed for NMS, published in the English literature in PUBMED and EMBASE databases from 1947-2022. RESULTS: 23 research papers, with data from 2648 clinically diagnosed and 171 pathologically verified cases of MSA were included, along with 238 controls. Mean age for MSA cases was 61.3 (9.2) years, mean disease duration 3.6 (2.7) years. 57.9% were male. Our analysis showed that the prevalence of cognitive issues in MSA varied widely (between 15-100%); dementia per se was uncommon, but assessment in advanced stages of MSA is impacted by unintelligible speech (which may be noted in a quarter of cases). The prevalence of depressive symptoms in MSA was between 44-88%. Sleep disturbances were reported by 17-89%, with REM-sleep behaviour disorder (RBD) rates as high as 75%. Pain was reported by 40-47% of patients: rheumatic or musculoskeletal sources of pain being commonest. Fatigue was reported by 29-60% of patients. Symptoms of autonomic failure in MSA were seen in 34-96.5% patients at baseline. CONCLUSION: In routine clinical practice, NMS in MSA are under-recognised by clinicians. These impact hugely on patient quality of life and contribute to their overall morbidity. A methodical ascertainment of these complaints will address an unmet need, and lead to a more holistic approach of care for individuals with MSA.
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Atrofia de Múltiplos Sistemas , Atrofia de Múltiplos Sistemas/epidemiologia , Atrofia de Múltiplos Sistemas/diagnóstico , Humanos , Prevalência , Transtornos do Sono-Vigília/epidemiologiaRESUMO
BACKGROUND: Use of nitrous oxide (N2O) gas for recreational purposes by young people is increasingly recognized as a public health hazard in the UK. METHODS: We looked at the hospital records of patients admitted over the last 4 years to a single neurological centre in Essex to determine the demographics, presentation, and management of patients presenting with symptoms of N2O toxicity from its recreational use. RESULTS: Of the 17 patients (mean age = 22.9 ± 3 years) admitted between September 2018 and October 2022, 70% were admitted between January and October 2022. All patients reported limb paraesthesiae and 16/17 reported (95%) imbalance; 11/17 (65%) showed objective limb weakness. Serum B12 concentration was low in 9/17 (53%). Plasma methylmalonic acid (n = 7) and homocysteine (n = 8) levels were elevated in all patients tested. Spinal cord Magnetic Resonance Imaging (MRI) imaging was abnormal in 10/17 (59%) patients. Nerve conduction studies were abnormal in 10/13 (77%) patients, with evidence of a symmetric, length-dependent, large fibre neuropathy. CONCLUSIONS: There has been a recent surge of cases with neurological complications of recreational N2O abuse in the UK, with a relatively greater rate in 2022. Greater awareness of this condition amongst clinicians and health regulators is urgently required to prevent harm from N2O misuse in young people.
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Doenças do Sistema Nervoso , Óxido Nitroso , Humanos , Adolescente , Adulto Jovem , Adulto , Óxido Nitroso/efeitos adversos , Londres/epidemiologia , Saúde Pública , Imageamento por Ressonância MagnéticaRESUMO
A middle-aged Asian man had gait difficulty progressing over several years. His speech had gradually become slurred with involuntary tongue biting. He was the product of a consanguineous marriage with no other relevant family history. MR scan of brain showed bilateral caudate atrophy. Nerve conduction studies showed a predominantly sensory peripheral neuropathy. Serum creatine kinase was slightly elevated but electromyography showed no evidence of myopathy. Three consecutive peripheral blood films were negative for acanthocytes. Whole-genome sequencing confirmed a mutation in VPS13A gene, consistent with autosomal recessive chorea-acanthocytosis.
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Neuroacantocitose , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neuroacantocitose/genética , Neuroacantocitose/diagnóstico , Proteínas de Transporte Vesicular/genéticaRESUMO
We report a case of conus medullaris syndrome presenting with lower limb and bladder symptoms. MR imaging showed an abnormality in the lowest part of the spinal cord as a first presentation of myelin oligodendrocyte glycoprotein (MOG)-associated disease. While such cord swelling can mimic a tumour, these patients respond well to corticosteroids, with good outcomes. MOG-associated disease is an immune-mediated syndrome distinct from aquaporin 4 antibody positive neuromyelitis optica syndrome and is now considered an independent entity. Although there can be overlapping phenotypes, there are also differences, and MOG-associated disease generally has a much better prognosis compared with aquaporin 4 antibody-positive neuromyelitis optica syndrome.
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Neuromielite Óptica , Compressão da Medula Espinal , Humanos , Neuromielite Óptica/complicações , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/tratamento farmacológico , Glicoproteína Mielina-Oligodendrócito , Aquaporina 4 , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/etiologia , AutoanticorposRESUMO
OBJECTIVES: To explore the genetics of four Parkinson's disease (PD) subtypes that have been previously described in two large cohorts of patients with recently diagnosed PD. These subtypes came from a data-driven cluster analysis of phenotypic variables. METHODS: We looked at the frequency of genetic mutations in glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 against our subtypes. Then we calculated Genetic Risk Scores (GRS) for PD, multiple system atrophy, progressive supranuclear palsy, Lewy body dementia, and Alzheimer's disease. These GRSs were regressed against the probability of belonging to a subtype in the two independent cohorts and we calculated q-values as an adjustment for multiple testing across four subtypes. We also carried out a Genome-Wide Association Study (GWAS) of belonging to a subtype. RESULTS: A severe disease subtype had the highest rates of patients carrying GBA mutations while the mild disease subtype had the lowest rates (p=0.009). Using the GRS, we found a severe disease subtype had a reduced genetic risk of PD (p=0.004 and q=0.015). In our GWAS no individual variants met genome wide significance (<5×10e-8) although four variants require further follow-up, meeting a threshold of <1×10e-6. CONCLUSIONS: We have found that four previously defined PD subtypes have different genetic determinants which will help to inform future studies looking at underlying disease mechanisms and pathogenesis in these different subtypes of disease.
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A 73-year-old woman developed cognitive decline over 1 year. MR scan of the brain showed a focal asymmetrical leukoencephalopathy involving the right frontal, temporal, parietal and occipital lobes. Extensive laboratory investigations found no cause but brain biopsy identified amyloid-beta-related angiitis (ABRA), a potentially treatable cause of rapid-onset dementia. We gave intravenous methylprednisolone and then two courses of intravenous cyclophosphamide, after which her cognitive skills gradually but significantly improved over several months.
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Demência , Vasculite , Idoso , Peptídeos beta-Amiloides/metabolismo , Biópsia , Encéfalo/patologia , Demência/complicações , Demência/diagnóstico por imagem , Demência/tratamento farmacológico , Feminino , Humanos , Vasculite/patologiaRESUMO
BACKGROUND: There are currently no treatments that stop or slow the progression of Parkinson's disease (PD). Case-control genome-wide association studies have identified variants associated with disease risk, but not progression. The objective of the current study was to identify genetic variants associated with PD progression. METHODS: We analyzed 3 large longitudinal cohorts: Tracking Parkinson's, Oxford Discovery, and the Parkinson's Progression Markers Initiative. We included clinical data for 3364 patients with 12,144 observations (mean follow-up 4.2 years). We used a new method in PD, following a similar approach in Huntington's disease, in which we combined multiple assessments using a principal components analysis to derive scores for composite, motor, and cognitive progression. These scores were analyzed in linear regression in genome-wide association studies. We also performed a targeted analysis of the 90 PD risk loci from the latest case-control meta-analysis. RESULTS: There was no overlap between variants associated with PD risk, from case-control studies, and PD age at onset versus PD progression. The APOE ε4 tagging variant, rs429358, was significantly associated with composite and cognitive progression in PD. Conditional analysis revealed several independent signals in the APOE locus for cognitive progression. No single variants were associated with motor progression. However, in gene-based analysis, ATP8B2, a phospholipid transporter related to vesicle formation, was nominally associated with motor progression (P = 5.3 × 10-6 ). CONCLUSIONS: We provide early evidence that this new method in PD improves measurement of symptom progression. We show that the APOE ε4 allele drives progressive cognitive impairment in PD. Replication of this method and results in independent cohorts are needed. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Doença de Parkinson , Biomarcadores , Cognição , Progressão da Doença , Estudo de Associação Genômica Ampla , Humanos , Doença de Parkinson/genéticaRESUMO
Our objective was to define the prevalence and clinical features of genetic Parkinson's disease in a large UK population-based cohort, the largest multicentre prospective clinico-genetic incident study in the world. We collected demographic data, Movement Disorder Society Unified Parkinson's Disease Rating Scale scores, and Montreal Cognitive Assessment scores. We analysed mutations in PRKN (parkin), PINK1, LRRK2 and SNCA in relation to age at symptom onset, family history and clinical features. Of the 2262 participants recruited to the Tracking Parkinson's study, 424 had young-onset Parkinson's disease (age at onset ≤ 50) and 1799 had late onset Parkinson's disease. A range of methods were used to genotype 2005 patients: 302 young-onset patients were fully genotyped with multiplex ligation-dependent probe amplification and either Sanger and/or exome sequencing; and 1701 late-onset patients were genotyped with the LRRK2 'Kompetitive' allele-specific polymerase chain reaction assay and/or exome sequencing (two patients had missing age at onset). We identified 29 (1.4%) patients carrying pathogenic mutations. Eighteen patients carried the G2019S or R1441C mutations in LRRK2, and one patient carried a heterozygous duplication in SNCA. In PRKN, we identified patients carrying deletions of exons 1, 4 and 5, and P113Xfs, R275W, G430D and R33X. In PINK1, two patients carried deletions in exon 1 and 5, and the W90Xfs point mutation. Eighteen per cent of patients with age at onset ≤30 and 7.4% of patients from large dominant families carried pathogenic Mendelian gene mutations. Of all young-onset patients, 10 (3.3%) carried biallelic mutations in PRKN or PINK1. Across the whole cohort, 18 patients (0.9%) carried pathogenic LRRK2 mutations and one (0.05%) carried an SNCA duplication. There is a significant burden of LRRK2 G2019S in patients with both apparently sporadic and familial disease. In young-onset patients, dominant and recessive mutations were equally common. There were no differences in clinical features between LRRK2 carriers and non-carriers. However, we did find that PRKN and PINK1 mutation carriers have distinctive clinical features compared to young-onset non-carriers, with more postural symptoms at diagnosis and less cognitive impairment, after adjusting for age and disease duration. This supports the idea that there is a distinct clinical profile of PRKN and PINK1-related Parkinson's disease. We estimate that there are approaching 1000 patients with a known genetic aetiology in the UK Parkinson's disease population. A small but significant number of patients carry causal variants in LRRK2, SNCA, PRKN and PINK1 that could potentially be targeted by new therapies, such as LRRK2 inhibitors.
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Análise da Randomização Mendeliana/métodos , Mutação/genética , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Vigilância da População/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Testes Genéticos/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Estudos Prospectivos , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Dementia is a common, debilitating feature of late Parkinson's disease (PD). PD dementia (PDD) is associated with α-synuclein propagation, but coexistent Alzheimer's disease (AD) pathology may coexist. Other pathologies (cerebrovascular, transactive response DNA-binding protein 43 (TDP-43)) may also influence cognition. We aimed to describe the neuropathology underlying dementia in PD. METHODS: Systematic review of autopsy studies published in English involving PD cases with dementia. Comparison groups included PD without dementia, AD, dementia with Lewy bodies (DLB) and healthy controls. RESULTS: 44 reports involving 2002 cases, 57.2% with dementia, met inclusion criteria. While limbic and neocortical α-synuclein pathology had the strongest association with dementia, between a fifth and a third of all PD cases in the largest studies had comorbid AD. In PD cases with dementia, tau pathology was moderate or severe in around a third, and amyloid-ß pathology was moderate or severe in over half. Amyloid-ß was associated with a more rapid cognitive decline and earlier mortality, and in the striatum, distinguished PDD from DLB. Positive correlations between multiple measures of α-synuclein, tau and amyloid-ß were found. Cerebrovascular and TDP-43 pathologies did not generally contribute to dementia in PD. TDP-43 and amyloid angiopathy correlated with coexistent Alzheimer pathology. CONCLUSIONS: While significant α-synuclein pathology is the main substrate of dementia in PD, coexistent pathologies are common. In particular, tau and amyloid-ß pathologies independently contribute to the development and pattern of cognitive decline in PD. Their presence should be assessed in future clinical trials where dementia is a key outcome measure. TRIAL REGISTRATION NUMBER: CRD42018088691.
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Doença de Alzheimer/epidemiologia , Doença de Alzheimer/patologia , Autopsia , Encéfalo/patologia , Demência/epidemiologia , Demência/patologia , Doença de Parkinson/epidemiologia , Doença de Parkinson/patologia , Autopsia/estatística & dados numéricos , Comorbidade , HumanosRESUMO
OBJECTIVES: To examine the influence of the glucocerebrosidase (GBA) mutation carrier state on age at onset of Parkinson's disease (PD), the motor phenotype and cognitive function at baseline assessment in a large cohort of UK patients. We also analysed the prevalence of mood and behavioural problems that may confound the assessment of cognitive function. METHODS: We prospectively recruited patients with PD in the Tracking Parkinson's study. We fully sequenced the GBA gene in all recently diagnosed patients (≤3.5 years). We examined cognitive (Montreal Cognitive Assessment) and motor (Movement Disorder Society Unified Parkinson's Disease Rating Scale part 3) function at a baseline assessment, at an average of 1.3 years after diagnosis. We used logistic regression to determine predictors of PD with mild cognitive impairment and PD with dementia. RESULTS: We studied 1893 patients with PD: 48 (2.5%) were heterozygous carriers for known Gaucher's disease (GD) causing pathogenic mutations; 117 (6.2%) had non-synonymous variants, previously associated with PD, and 28 (1.5%) patients carried variants of unknown significance in the GBA gene. L444P was the most common pathogenic GBA mutation. Patients with pathogenic GBA mutations were on average 5 years younger at disease onset compared with non-carriers (P=0.02). PD patients with GD-causing mutations did not have an increased family risk of PD. Patients with GBA mutations were more likely to present with the postural instability gait difficulty phenotype compared with non-carriers (P=0.02). Patients carrying pathogenic mutations in GBA had more advanced Hoehn and Yahr stage after adjustment for age and disease duration compared with non-carriers (P=0.005). There were no differences in cognitive function between GBA mutation carriers and non-carriers at this early disease stage. CONCLUSIONS: Our study confirms the influence of GBA mutations on the age of onset, disease severity and motor phenotype in patients with PD. Cognition did not differ between GBA mutation carriers and non-carriers at baseline, implying that cognitive impairment/dementia, reported in other studies at a later disease stage, is not present in recently diagnosed cases. This offers an important window of opportunity for potential disease-modifying therapy that may protect against the development of dementia in GBA-PD. CLINICAL TRIAL REGISTRATION: NCT02881099; Results.
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Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Glucosilceramidase/genética , Heterozigoto , Mutação/genética , Doença de Parkinson/genética , Idade de Início , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Estudos Prospectivos , Reino UnidoRESUMO
OBJECTIVES: To use a data-driven approach to determine the existence and natural history of subtypes of Parkinson's disease (PD) using two large independent cohorts of patients newly diagnosed with this condition. METHODS: 1601 and 944 patients with idiopathic PD, from Tracking Parkinson's and Discovery cohorts, respectively, were evaluated in motor, cognitive and non-motor domains at the baseline assessment. Patients were recently diagnosed at entry (within 3.5 years of diagnosis) and were followed up every 18 months. We used a factor analysis followed by a k-means cluster analysis, while prognosis was measured using random slope and intercept models. RESULTS: We identified four clusters: (1)  fast motor progression with symmetrical motor disease, poor olfaction, cognition and postural hypotension; (2) mild motor and non-motor disease with intermediate motor progression; (3) severe motor disease, poor psychological well-being and  poor sleep with an intermediate motor progression; (4) slow motor progression with tremor-dominant, unilateral disease. Clusters were moderately to substantially stable across the two cohorts (kappa 0.58). Cluster 1 had the fastest motor progression in Tracking Parkinson's at 3.2 (95% CI 2.8 to 3.6) UPDRS III points per year while cluster 4 had the slowest at 0.6 (0.1-1.1). In Tracking Parkinson's, cluster 2 had the largest response to levodopa 36.3% and cluster 4 the lowest 28.8%. CONCLUSIONS: We have found four novel clusters that replicated well across two independent early PD cohorts and were associated with levodopa response and motor progression rates. This has potential implications for better understanding disease pathophysiology and the relevance of patient stratification in future clinical trials.
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Doença de Parkinson/classificação , Idoso , Progressão da Doença , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Testes Neuropsicológicos , Doença de Parkinson/tratamento farmacológico , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Índice de Gravidade de DoençaRESUMO
We discuss the assessment and differential diagnoses of a middle-aged man who presented with trismus, double vision and behavioural problems. MRI scan of the brain was initially normal, but a month later showed high signal in the hippocampal region on fluid attenuated inversion recovery sequence (FLAIR) imaging. We suspected a paraneoplastic brainstem encephalitis because of his smoking history, rapidly progressive symptoms and abnormal brainstem signs. A positron emission tomography-CT scan identified abnormal subcarinal nodes, shown on biopsy to be metastatic small cell lung cancer. He is currently undergoing treatment with chemotherapy and radiotherapy.
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Encefalite/etiologia , Neoplasias Pulmonares/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/complicações , Carcinoma de Pequenas Células do Pulmão/complicações , Trismo/etiologia , Tronco Encefálico/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
An elderly Caucasian man presented with a 10-month history of proximal myopathy and dysphagia. His serum creatine kinase (CK) was elevated at 877 U/L (normal 40-320) and electromyography confirmed a myopathic process. Blood and urine tests suggested myeloma; bone marrow examination showed 30% plasma cells and stained positive for amyloid. The muscle biopsy was initially reported as normal but in the light of the bone marrow report, the biopsy specimen was stained for amyloid, which was positive. We diagnosed systemic amyloidosis causing a myopathy and have started treatment for myeloma.
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Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Distrofia Muscular do Cíngulo dos Membros/complicações , Idoso , Medula Óssea/patologia , Creatina Quinase/sangue , Diagnóstico Diferencial , Eletrocardiografia , Humanos , Masculino , Distrofia Muscular do Cíngulo dos Membros/sangue , Distrofia Muscular do Cíngulo dos Membros/diagnóstico por imagem , Tomografia por Emissão de PósitronsRESUMO
We discuss the clinical presentation and assessment of a middle aged previously fit and well man who presented with two episodes of syncope to the cardiologists followed by the development of a rapidly progressive parkinsonian syndrome a couple of years later, which was not responsive to standard dopaminergic replacement therapies. Magnetic resonance imaging scan of the brain was normal and a DAT SPECT scan showed reduced dopamine uptake in the basal ganglia. On further enquiry, a family history of a similar presentation in his first cousin was elicited and that cousin had tested positive for a mutation in the PRNP gene. Subsequently, he also tested positive for A117V mutation in the PRNP gene, confirming familial Creutzfeld Jakob disease. Familial Creutzfeld Jakob disease presenting with parkinsonism is rare in clinical practice, but it is something that neurologists and geriatricians running movement disorder clinics should be aware of, as this is a rapidly progressive and uniformly fatal condition with inheritance risks to family members.
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Síndrome de Creutzfeldt-Jakob/genética , Anamnese , Transtornos Parkinsonianos/genética , Proteínas Priônicas/genética , Adulto , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/fisiopatologia , Progressão da Doença , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos Parkinsonianos/etiologia , Transtornos Parkinsonianos/fisiopatologiaRESUMO
BACKGROUND: Cardiovascular disease (CVD) influences phenotypic variation in Parkinson's disease (PD), and is usually an indication for statin therapy. It is less clear whether cardiovascular risk factors influence PD phenotype, and if statins are prescribed appropriately. OBJECTIVES: To quantify vascular risk and statin use in recent-onset PD, and examine the relationship between vascular risk, PD severity and phenotype. METHODS: Cardiovascular risk was quantified using the QRISK2 calculator (high ≥20%, medium ≥10 and <20%, low risk <10%). Motor severity and phenotype were assessed using the Movement Disorder Society Unified PD Rating Scale (UPDRS) and cognition by the Montreal cognitive assessment. RESULTS: In 2909 individuals with recent-onset PD, the mean age was 67.5â years (SD 9.3), 63.5% were men and the mean disease duration was 1.3â years (SD 0.9). 33.8% of cases had high vascular risk, 28.7% medium risk, and 22.3% low risk, while 15.2% of cases had established CVD. Increasing vascular risk and CVD were associated with older age (p<0.001), worse motor score (p<0.001), more cognitive impairment (p<0.001) and worse motor phenotype (p=0.021). Statins were prescribed in 37.2% with high vascular risk, 15.1% with medium vascular risk and 6.5% with low vascular risk, which compared with statin usage in 75.3% of those with CVD. CONCLUSIONS: Over 60% of recent-onset PD patients have high or medium cardiovascular risk (meriting statin usage), which is associated with a worse motor and cognitive phenotype. Statins are underused in these patients, compared with those with vascular disease, which is a missed opportunity for preventive treatment. TRIAL REGISTRATION NUMBER: GN11NE062, NCT02881099.
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Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Uso de Medicamentos/estatística & dados numéricos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Fatores Etários , Idoso , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Comorbidade , Estudos Transversais , Inglaterra , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Fenótipo , Medição de RiscoRESUMO
OBJECTIVE: The purpose of this study was to examine the relationship between vascular disease (and vascular risk factors), cognition and motor phenotype in Parkinson's disease (PD). METHODS: Recently diagnosed PD cases were enrolled in a multicenter prospective observational longitudinal cohort study. Montreal cognitive assessment (normal >23, mild cognitive impairment 22 to 23 or lower but without functional impairment, and dementia 21 or less with functional impairment) and Movement Disorder Society Unified PD Rating Scale part 3 (UPDRS 3) scores were analyzed in relation to a history of vascular events and risk factors. RESULTS: In 1759 PD cases, mean age 67.5 (standard deviation 9.3) years, mean disease duration 1.3 (standard deviation 0.9) years, 65.2% were men, 4.7% had a history of prior stroke or transient ischemic attack, and 12.5% had cardiac disease (angina, myocardial infarction, heart failure). In cases without a history of vascular disease, hypertension was recorded in 30.4%, high cholesterol 27.3%, obesity 20.7%, diabetes 7.2%, and cigarette smoking in 4.6%. Patients with prior stroke or transient ischemic attack were more likely to have cognitive impairment (42% vs 25%) and postural instability gait difficulty (53.5% vs 39.5%), but these findings were not significant after adjustment for age, sex, and disease duration (P = .075). The presence of more than 2 vascular risks was associated with worse UPDRS 3 motor scores (beta coefficient 4.05, 95% confidence interval 1.48, 6.61, p = .002) and with cognitive impairment (ordinal odds ratio 2.24, 95% confidence interval 1.34, 3.74, p = .002). In 842 patients (47.8%) with structural brain imaging, white matter leukoaraiosis, but not lacunar or territorial infarction, was associated with impaired cognition (p = .006) and postural instability gait difficulty (p = .010). CONCLUSION: Vascular comorbidity is significantly associated with cognitive and gait impairment in patients with early PD, which may have prognostic and treatment implications. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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Disfunção Cognitiva/fisiopatologia , Demência/fisiopatologia , Transtornos Neurológicos da Marcha/fisiopatologia , Doença de Parkinson/fisiopatologia , Doenças Vasculares/fisiopatologia , Idoso , Disfunção Cognitiva/epidemiologia , Comorbidade , Demência/epidemiologia , Feminino , Transtornos Neurológicos da Marcha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Estudos Prospectivos , Fatores de Risco , Reino Unido/epidemiologia , Doenças Vasculares/epidemiologiaRESUMO
Dementia is a broad term used to describe several chronic progressive neurological disorders that adversely affect higher mental functions including memory, language, behaviour, abstract thinking, comprehension, calculation, learning capacity and judgement. Alzheimer's disease is the most common form of dementia but other neurological conditions such as Parkinson's disease, cerebrovascular disease and chronic infections such as syphilis can also lead to the clinical syndrome of dementia. Initial investigations should always focus on finding any treatable cause for dementia such as HIV, structural lesions such as subdural haematomas or specific nutritional deficiency states such as that due to vitamin B12 and treated appropriately. Where no treatable or reversible aetiology is found, a referral to a specialist should be considered who may initiate further investigations including magnetic resonance imaging or perfusion single-photon emission computerised tomography scans of the brain, and sometimes cerebrospinal fluid examination or an electroencephalogram.
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Inibidores da Colinesterase/uso terapêutico , Demência/tratamento farmacológico , Demência/etiologia , Nootrópicos/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Análise Custo-Benefício , Humanos , Escócia/epidemiologia , Resultado do TratamentoRESUMO
Progressive myoclonic epilepsies are a group of disorders characterised by a relentlessly progressive disease course until death; treatment-resistant epilepsy is just a part of the phenotype. This umbrella term encompasses many diverse conditions, ranging from Lafora body disease to Gaucher's disease. These diseases as a group are important because of a generally poor response to antiepileptic medication, an overall poor prognosis and inheritance risks to siblings or offspring (where there is a proven genetic cause). A correct diagnosis also helps patients and their families to accept and understand the nature of their disease, even if incurable. Here, we discuss the phenotypes of these disorders and summarise the relevant specific investigations to identify the underlying cause.
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Epilepsias Mioclônicas Progressivas , HumanosRESUMO
There are 90 independent genome-wide significant genetic risk variants for Parkinson's disease (PD) but currently only five nominated loci for PD progression. The biology of PD progression is likely to be of central importance in defining mechanisms that can be used to develop new treatments. We studied 6766 PD patients, over 15,340 visits with a mean follow-up of between 4.2 and 15.7 years and carried out genome-wide survival studies for time to a motor progression endpoint, defined by reaching Hoehn and Yahr stage 3 or greater, and death (mortality). There was a robust effect of the APOE ε4 allele on mortality in PD. We also identified a locus within the TBXAS1 gene encoding thromboxane A synthase 1 associated with mortality in PD. We also report 4 independent loci associated with motor progression in or near MORN1, ASNS, PDE5A, and XPO1. Only the non-Gaucher disease causing GBA1 PD risk variant E326K, of the known PD risk variants, was associated with mortality in PD. Further work is needed to understand the links between these genomic variants and the underlying disease biology. However, these may represent new candidates for disease modification in PD.
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Structural and functional imaging prior to surgery in drug-resistant focal epilepsy, has an important role to play alongside electroencephalography (EEG) techniques, in planning the surgical approach and predicting post-operative outcome. This paper reviews the role of structural and functional imaging of the brain, namely computed tomography (CT), magnetic resonance imaging (MRI), functional MRI (fMRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging in the preoperative work-up of people with medically refractory epilepsy. In MRI-negative patients, the precise localisation of the epileptogenic zone may be established by demonstrating hypometabolism on PET imaging or hyperperfusion on SPECT imaging in the area surrounding the seizure focus. These imaging modalities are far less invasive than intracranial EEG, which is the gold standard but requires surgical placement of electrodes or recording grids. Even when intracranial EEG is needed, PET or SPECT imaging can assist in the planning of EEG electrode placement, due to its' limited spatial sampling. Multimodal imaging techniques now allow the multidisciplinary epilepsy surgery team to identify and better characterise focal pathology, determine its' relationship to eloquent areas of the brain and the degree of interconnectedness within both physiological and pathological networks, as well as improve planning and surgical outcomes for patients. This paper will update the reader on this whole field and provide them with a practical guide, to aid them in the selection of appropriate investigations, interpretation of the findings and facilitating patient discussions in individuals with drug-resistant focal epilepsy.