RESUMO
BACKGROUND: Mild parkinsonian signs (MPS) are frequent in the elderly population and associated with the presence of risk markers for Parkinson's disease (PD). Both MPS and non-motor signs may be present in prodromal PD and may significantly impair quality of life (QoL). OBJECTIVE: To disentangle the contribution of motor impairment and extra-motor manifestations to QoL in subjects with MPS (n=63), manifest PD (n=69), disorders with motor symptoms due to non-neurodegenerative diseases (n=213) and healthy controls (n=258). METHODS: Subjects with MPS, healthy controls, disease controls (patients with motor impairment due to, eg, arthrosis and spondylosis), and PD patients (total n=603) were selected from a large epidemiological longitudinal study, the EPIPARK cohort. Motor function was determined using the UPDRSIII protocol, and information on depressive symptoms, anxiety, sleep, and QoL was assessed via rating scales and data were analyzed. RESULTS: Depressive symptoms, anxiety, and sleep problems were equally frequent in the MPS group and controls. Health-related QoL was slightly reduced in the MPS group. Motor impairment and its extent was comparable between the MPS group and disease controls (UPDRSIII 5-6 points). Higher motor dysfunction was associated with lower QoL. Depressive symptoms, but not anxiety and daytime sleepiness, was significant predictors of general QoL, independent of motor function. CONCLUSIONS: Quality of life is slightly decreased in an elderly population with MPS. QoL is associated with severity of motor impairment but also with non-motor aspects, ie, depressive symptoms. Follow-up studies in large cohorts are warranted to determine the natural course of MPS and its impact on QoL.
Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Doença de Parkinson/complicações , Qualidade de Vida , Transtornos do Sono-Vigília/epidemiologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Doença de Parkinson/epidemiologia , Doença de Parkinson/psicologiaRESUMO
BACKGROUND: Psychiatric symptoms/syndromes such as depression, apathy, anxiety or psychotic episodes are present in a range of neurological disorders including Parkinson's disease. The Structured Clinical Interview for DSM-IV (SCID) represents the gold standard for the assessment of psychiatric disorders but is often too time-consuming for application in clinical practice. METHODS: 66 participants were examined using the screening items and the first two questions of section A of the SCID as well as the complete version of the SCID, part I. The accuracy of the screening and the complete SCID was evaluated, and logistic regression was conducted to analyze factors associated with measure disagreement between the two procedures. RESULTS: Overall, psychiatric disorders were identified by screening in 40/66 (60.6%), as against 31/66 (47.0%) using the complete SCID. Compared to the complete SCID, the sensitivity and specificity of the screening items were 88% and 59%, respectively. CONCLUSION: Based on its good sensitivity, the SCID screening may be used in clinical practice to yield an overview of psychiatric disorders that may require treatment. Due to its moderate specificity, however, the complete version of the SCID should be subsequently used in cases whenever the SCID screening is positive. In any case, the SCID screening must be regarded as inadequate for the detection of psychotic symptoms.
Assuntos
Manual Diagnóstico e Estatístico de Transtornos Mentais , Entrevista Psicológica , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Reprodutibilidade dos Testes , Fatores SocioeconômicosRESUMO
OBJECTIVE: While several genes have been identified to cause Parkinson's disease (PD), monogenic forms explain only a small proportion of cases. We report clinical and genetic results in a large family with late-onset autosomal dominant PD. METHODS: Thirty-eight family members of a five-generation Northern German PD family underwent a detailed neurologic examination, and transcranial sonography was performed in fifteen of them. Comprehensive mutation analysis of known PD-causing genes and a genome-wide linkage analysis were performed. RESULTS: Late-onset definite PD was found in five subjects with a mean age at onset of 63 years. Another six individuals presented either with probable/possible PD or with subtle parkinsonian signs. Six members with a mean age of 79 years had an essential tremor phenotype. Mode of PD inheritance was compatible with autosomal dominant transmission. One of three examined patients with definite PD demonstrated an increased area of substantia nigra hyperechogenicity upon transcranial sonography. Comprehensive linkage and mutational analysis excluded mutations in known PD-causing genes. Genome-wide linkage analysis suggested a putative disease gene in an 11.3-Mb region on chromosome 7p15-21.1 with a multipoint LOD score of 2.0. CONCLUSIONS: The findings in this family further demonstrate genetic heterogeneity in familial autosomal dominant late-onset PD.
Assuntos
Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/patologia , Idade de Início , Idoso , Encéfalo/patologia , Análise Mutacional de DNA , Feminino , Alemanha , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , LinhagemAssuntos
Autoanticorpos/metabolismo , Autoantígenos/imunologia , Distonina/imunologia , Esclerose Múltipla/imunologia , Colágenos não Fibrilares/imunologia , Doença de Parkinson/imunologia , Adulto , Idoso , Derme/imunologia , Derme/metabolismo , Epiderme/imunologia , Epiderme/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Colágeno Tipo XVIIRESUMO
Neurodegenerative disorders, such as Huntington's disease, spinocerebellar ataxias, Parkinson's disease or Alzheimer's disease, manifest in adult age with insidiously developing, slowly progressing symptoms. At this stage, most patients consult a doctor, and a definite diagnosis can be made. It is, however, well established that the manifest disease is preceded by a presymptomatic disease stage that may last for years. A striking example is Parkinson's disease, in which more than half of the dopaminergic neurons of the substantia nigra are lost before motor symptoms appear. Studies of the presymptomatic stage of neurodegenerative disorders are pivotal for an advanced understanding of these disorders and the development of preventive strategies aimed at postponing the clinical onset of these disorders. It is therefore important to identify the earliest and most sensitive clinical signs and biological markers that herald the onset of the illness. Furthermore, studies of presymptomatic disease stages are important because they may help to unravel compensatory mechanisms responsible for apparently normal brain function despite ongoing neurodegeneration.
Assuntos
Doenças Assintomáticas , Transtornos Heredodegenerativos do Sistema Nervoso/diagnóstico , Exame Neurológico , Adulto , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Biomarcadores , Encéfalo/patologia , Progressão da Doença , Diagnóstico Precoce , Endofenótipos , Marcadores Genéticos/genética , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Humanos , Doença de Huntington/diagnóstico , Doença de Huntington/genética , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , Expansão das Repetições de Trinucleotídeos/genéticaRESUMO
Transcranial sonography (TCS) of the brain parenchyma is a non-invasive and easily applicable neuroimaging technique which is used as a diagnostic tool in Parkinson's disease. Up to 90% of patients with idiopathic Parkinson's disease but only 10-15% of the healthy population show an abnormal echogenicity (hyperechogenicity) of the substantia nigra (SN). TCS has been demonstrated to be a useful tool in the differential diagnosis of patients with essential tremor or atypical parkinsonian syndromes, including the parkinsonian variant of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) where hyperechogenicity of the SN is less frequent. Abnormal echogenicity of the SN has been found in almost all investigated monogenic types of parkinsonism and even in asymptomatic mutation carriers. The nature of the pathological substrate leading to the abnormal echogenicity of the SN remains elusive. Longitudinal studies of asymptomatic subjects with abnormal echogenicity of the SN are still ongoing to evaluate the risk for developing Parkinson's disease in the future in these subjects.
Assuntos
Encéfalo/patologia , Ecoencefalografia/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Doença por Corpos de Lewy , Doença de Parkinson/diagnóstico por imagem , Gânglios da Base/diagnóstico por imagem , Diagnóstico Diferencial , Diagnóstico Precoce , Tremor Essencial/diagnóstico por imagem , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Imageamento por Ressonância Magnética , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Transtornos Parkinsonianos/diagnóstico por imagem , Sensibilidade e Especificidade , Substância Negra/diagnóstico por imagem , Paralisia Supranuclear Progressiva/diagnóstico por imagemRESUMO
Fatigue is a common problem in patients suffering from multiple sclerosis (MS). The presented case demonstrated concomitant severe central sleep apnea. Selection of the optimal ventilation modus was complex but proved successful. Given that daytime sleepiness is a frequent symptom in MS patients and that effective treatment options are available, sleep apnea should be considered and further classified by polysomnography in order to improve patients' quality of life.
Assuntos
Esclerose Múltipla/diagnóstico , Esclerose Múltipla/reabilitação , Polissonografia/métodos , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Apneia do Sono Tipo Central/complicações , Resultado do TratamentoRESUMO
Imaging of the brain structure with transcranial ultrasound has become an important tool for the diagnosis and differential diagnosis of Parkinson's Disease. In up to 90 % of parkinsonian patients abnormal echogenity of the substantia nigra could be demonstrated. Particularly in the early diagnosis in subjects with only very mild extrapyramidal features and in the differential diagnosis to other neurodegenerative disorders with parkinsonian features, such as the parkinsonian variant of multisystematrophy (MSA-P) and progressive supranuclear paralysis (PSP) ultrasound has a high diagnostic yield. Because of a prevalence of about 10 % in the normal population, the evidence of an abnormal echogenity of the substantia nigra has to be interpreted carefully in the context of a clinical examination. Although there are a number of studies indicating that in some of these subjects a vulnerability of the nigrostriatal system can be found, the meaning of an abnormal echogenicity of the substantia nigra in the healthy population needs to be further elucidated in already ongoing research projects.
Assuntos
Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/diagnóstico , Ultrassonografia Doppler Transcraniana , Encéfalo/patologia , Diagnóstico Diferencial , Humanos , Atrofia de Múltiplos Sistemas/diagnóstico , Doença de Parkinson/patologia , Transtornos Parkinsonianos/diagnóstico , Paralisia Supranuclear Progressiva/diagnósticoRESUMO
BACKGROUND: It is unclear whether sensory symptoms in Parkinson disease (PD) are of primary or of secondary origin attributable to motor symptoms such as rigidity and bradykinesia. OBJECTIVE: The aim of this study was to elucidate whether sensory abnormalities are present and may precede motor symptoms in familial parkinsonism by characterizing sensory function in symptomatic and asymptomatic PINK1 mutation carriers. METHODS: Fourteen family members with PINK1 mutation and 14 healthy controls were examined clinically, with nerve conduction studies and quantitative sensory testing (QST). RESULTS: Thresholds for mechanical detection, mechanical pain and pressure pain were higher in PINK1 mutation carriers compared to controls. Higher thresholds for mechanical detection, mechanical pain and pressure pain were even found in asymptomatic, clinically not or only mildly affected PINK1 mutation carriers. CONCLUSIONS: Data suggest that PINK1-associated PD is associated with a primary hypofunction of nociceptive and non-nociceptive afferent systems that can already be found at the time when motor signs of PD are only subtle. As nerve conduction studies did not reveal differences between PINK1 mutation carriers and controls, we propose that the somatosensory impairment is related to abnormal central somatosensory processing.
Assuntos
Mutação/fisiologia , Doença de Parkinson/genética , Proteínas Quinases/genética , Transtornos de Sensação/genética , Adulto , Idoso , Antiparkinsonianos/uso terapêutico , Família , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Limiar da Dor/fisiologia , Doença de Parkinson/tratamento farmacológico , Estimulação Física , Transtornos de Sensação/tratamento farmacológicoRESUMO
BACKGROUND: Primary focal dystonia (PFD) is characterised by motor symptoms. Frequent co-occurrence of abnormal mental conditions has been mentioned for decades but is less well defined. In this study, prevalence rates of psychiatric disorders, personality disorders and traits in a large cohort of patients with PFD were evaluated. METHODS: Prevalence rates of clinical psychiatric diagnoses in 86 PFD patients were compared with a population based sample (n = 3943) using a multiple regression approach. Furthermore, participants were evaluated for personality traits with the 5 Factor Personality Inventory. RESULTS: Lifetime prevalence for any psychiatric or personality disorder was 70.9%. More specifically, axis I disorders occurred at a 4.5-fold increased chance. Highest odds ratios were found for social phobia (OR 21.6), agoraphobia (OR 16.7) and panic disorder (OR 11.5). Furthermore, an increased prevalence rate of 32.6% for anxious personality disorders comprising obsessive-compulsive (22.1%) and avoidant personality disorders (16.3%) were found. Except for social phobia, psychiatric disorders manifested prior to the occurrence of dystonia symptoms. In the self-rating of personality traits, PFD patients demonstrated pronounced agreeableness, conscientiousness and reduced openness. CONCLUSIONS: Patients with PFD show distinct neuropsychiatric and personality profiles of the anxiety spectrum. PFD should therefore be viewed as a neuropsychiatric disorder rather than a pure movement disorder.
Assuntos
Sintomas Afetivos/epidemiologia , Distúrbios Distônicos/psicologia , Transtornos Mentais/epidemiologia , Personalidade , Adulto , Idade de Início , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Numerous factors determine stability of reverse total shoulder arthroplasty. The effect of the conjoint tendon in relation to stability remains unknown. In this biomechanical study, we evaluated the influence of the conjoint tendon on the anterior stability of reverse total shoulder arthroplasty with a hemispherical glenosphere and a glenosphere with 9â¯mm lateralisation. METHODS: A reverse total shoulder arthroplasty was implanted in 6 human cadaveric shoulders. The anterior stability was evaluated using a shoulder simulator. Two conditions, intact and dissected conjoint tendon, and 2 component configurations, a hemispherical glenosphere and a glenosphere with 9â¯mm lateralisation, were tested in each specimen. Testing of anterior stability was performed in 30° and 60° of abduction, with 0° and 30° of external rotation in the glenohumeral joint. FINDINGS: The conjoint tendon showed a significant influence on the anterior stability with a hemispherical glenosphere in 30° and 60° with neutral rotation (pâ¯=â¯0.028) as well as 30° abduction with 30° (pâ¯=â¯0.028) external rotation. The 9â¯mm lateralised glenosphere stabilized significantly reverse total shoulder arthroplasty with resected conjoint tendon compared to the hemispherical glenosphere with resected conjoint tendon (pâ¯=â¯0.028). INTERPRETATION: In a biomechanical setting the conjoint tendon has a stabilizing influence on the anterior stability of the reverse total shoulder arthroplasty with a hemispherical glenosphere in an abducted arm position, but this stabilizing effect was not seen with the lateralised glenosphere. The single influence of the lateralisation of the glenosphere on anterior stability was shown in cases of resected conjoint tendon.
Assuntos
Artroplastia do Ombro/métodos , Articulação do Ombro/cirurgia , Ombro/cirurgia , Tendões/cirurgia , Idoso , Fenômenos Biomecânicos , Cadáver , Humanos , Pessoa de Meia-Idade , Desenho de Prótese , Amplitude de Movimento Articular , Rotação , Articulação do Ombro/fisiopatologia , Tendões/fisiopatologiaRESUMO
Myoclonus-dystonia (M-D) is an autosomal-dominant movement disorder caused by mutations in SGCE. We investigated the frequency and type of SGCE mutations with emphasis on gene dosage alterations and explored the associated phenotypes. We tested 35 M-D index patients by multiplex ligation-dependent probe amplification (MLPA) and genomic sequencing. Mutations were found in 26% (9/35) of the cases, all but three with definite M-D. Two heterozygous deletions of the entire SGCE gene and flanking DNA and a heterozygous deletion of exon 2 only were detected, accounting for 33% (3/9) of the mutations found. Both large deletions contained COL1A2 and were additionally associated with joint problems. Further, we discovered one novel small deletion (c.771_772delAT, p.C258X) and four recurrent point mutations (c.289C>T, p.R97X; c.304C>T, p.R102X; c.709C>T, p.R237X; c.1114C>T, p.R372X). A Medline search identified 22 articles on SGCE mutational screening. Sixty-four unrelated M-D patients were described with 41 different mutations. No genotype-phenotype association was found, except in patients with deletions encompassing additional genes. In conclusion, a rigorous clinical preselection of patients and careful accounting for non-motor signs should precede mutational tests. Gene dosage studies should be included in routine SGCE genetic testing.
Assuntos
Deleção de Genes , Mioclonia/genética , Sarcoglicanas/genética , Adolescente , Adulto , Idoso , Sequência de Bases , Criança , Pré-Escolar , Análise Mutacional de DNA , Demografia , Éxons/genética , Feminino , Genoma Humano , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Fenótipo , Literatura de Revisão como AssuntoRESUMO
OBJECTIVE: To investigate substantia nigra (SN) echogenicity in members of a family with homozygous and heterozygous PTEN induced kinase (PINK1) mutations with or without signs of Parkinson's disease (PD). METHODS: Transcranial sonography (TCS) was used to investigate 20 members of a family with PINK1 mutations, including four homozygous and 11 heterozygous mutation carriers and five individuals with no mutation. For comparison, a healthy control group of 18 subjects without a positive family history of PD (control group) and a healthy control group of 15 subjects with a positive family history of sporadic PD (relative group) were investigated. For statistical analysis, the larger area of the two SNs echogenicity (aSNmax) of each individual was selected. RESULTS: A significantly increased aSNmax was found for all subgroups compared with the control group. The group of homozygous carriers of a PINK1 mutation had a significantly increased aSNmax compared with all of the other subgroups, except the group of heterozygous mutation carriers. CONCLUSIONS: These findings in carriers of a PINK1 mutation are comparable with those in carriers of Parkin mutations and non-genetic PD. The increased aSNmax in family members without a mutation suggests an additional contributing factor independent of the PINK1 mutation that may also play a role in relatives of patients with sporadic PD.
Assuntos
Heterozigoto , Homozigoto , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/genética , Mutação Puntual/genética , Proteínas Quinases/genética , Substância Negra/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , UltrassonografiaRESUMO
To further evaluate (1) transcranial sonography (TCS) for (pre)clinical diagnosis of Parkinson's disease (PD) and (2) to examine asymptomatic carriers of Parkin mutations we investigated substantia nigra (SN) hyperechogenicity in PD patients and unaffected subjects with and without Parkin mutations. The area (aSN) of the hyperechogenic SN were calculated bilaterally and study subjects were assigned to high versus low value groups. Eleven of the (affected and unaffected) mutation carriers had previously undergone 18-fluoro-dopa-(FDOPA)-PET scans. Fifty-eight individuals were investigated, including 24 with clinically definite and 34 without symptoms or signs of PD. Of the patients, three had one mutated and six had two mutated Parkin alleles. Of the unaffected subjects, 13 carried a single Parkin mutated allele. After dichotomization, 21 subjects had high and 37 subjects low values of mean aSN. Regarding the clinical status, 13 (62%) of the individuals with a high mean aSN had PD,while 26 (70%) of the study subjects with low values did not show signs of PD (p = 0.0393). Similarly, probands with high mean aSN values more frequently carried Parkin mutations (58%) than probands with low values (27%, p = 0.0234). A negative correlation between FDOPA uptake in the posterior putamen and maximum aSN was found in the group of mutation carriers (r = -0.809, p = 0.0234). In conclusion, hyperechogenicity of the SN is found in both idiopathic and Parkin-associated PD. Further strengthening the notion of a potential relationship between SN hyperechogenicity and Parkin mutational status, a larger aSN was associated with an increasing number of mutated alleles in our study.
Assuntos
Predisposição Genética para Doença , Mutação , Doença de Parkinson/genética , Substância Negra/diagnóstico por imagem , Ubiquitina-Proteína Ligases/genética , Ultrassonografia Doppler Transcraniana/métodos , Adulto , Alelos , Estudos de Coortes , Feminino , Radioisótopos de Flúor , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Curva ROCRESUMO
Spinocerebellar ataxia 17 (SCA17) is a rare genetic disorder characterized by cerebellar, extrapyramidal, pyramidal as well as psychiatric signs. The pathoanatomical basis of this disorder is still not well known. A total of 12 patients and 12 age- and sex-matched controls were examined by in vivo MRI voxel-based morphometry (VBM). Besides general patterns of disease-related brain atrophy, characteristic syndrome-related morphological changes in SCA17 patients were studied. In comparison with normal controls, SCA17 patients showed a pattern of degeneration of the grey matter centred around mesial cerebellar structures, occipito-parietal structures, the anterior putamen bilaterally, the thalamus and other parts of the motor network, reflecting the cerebellar, pyramidal and extrapyramidal signs. A correlation analysis revealed a clear association between the clinical cerebellar, extrapyramidal and psychiatric scores and degeneration in specific areas. Two degeneration patterns were found as follows: regarding motor dysfunction, atrophy of the grey matter involved mainly the cerebellum and other motor networks, in particular the basal ganglia. In contrast, correlations with psychiatric scores revealed grey matter degeneration patterns in the frontal and temporal lobe, the cuneus and cingulum. Most interestingly, there was a highly significant correlation between the clinical Mini-Mental State Examination scores and atrophy of the nucleus accumbens, probably accounting for the leading psychiatric signs.
Assuntos
Ataxias Espinocerebelares/patologia , Adulto , Atrofia , Gânglios da Base/patologia , Encéfalo/patologia , Estudos de Casos e Controles , Cerebelo/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Testes Neuropsicológicos , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/patologia , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/patologia , Paraplegia Espástica Hereditária/patologia , Paraplegia Espástica Hereditária/fisiopatologia , Paraplegia Espástica Hereditária/psicologia , Ataxias Espinocerebelares/fisiopatologia , Ataxias Espinocerebelares/psicologia , Telencéfalo/patologia , Fatores de TempoAssuntos
Distúrbios do Metabolismo do Ferro/diagnóstico por imagem , Distúrbios do Metabolismo do Ferro/diagnóstico , Distrofias Neuroaxonais/diagnóstico por imagem , Distrofias Neuroaxonais/diagnóstico , Idoso , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/patologia , Evolução Fatal , Humanos , Distúrbios do Metabolismo do Ferro/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Distrofias Neuroaxonais/patologia , Ultrassonografia Doppler Transcraniana/métodosRESUMO
Mutations in the Parkin gene are the most common known single cause of early-onset parkinsonism. It has been shown that asymptomatic carriers with a single mutant allele have latent presynaptic dopaminergic dysfunction in the striatum. Here we used functional MRI to map movement-related neuronal activity during internally selected or externally determined finger movements in 12 asymptomatic carriers of a Parkin mutation and 12 healthy non-carriers. Mean response times were 63 ms shorter during internally selected movements than during externally guided movements (P = 0.003). There were no differences in mean response times between groups (P > 0.2). Compared with externally determined movements, the internal selection of movements led to a stronger activation of rostral motor areas, including the rostral cingulate motor area (rCMA), rostral supplementary motor area, medial and dorsolateral prefrontal cortices. The genotype had a significant impact on movement-related activation patterns. Asymptomatic carriers showed a stronger increase in movement-related activity in the right rCMA and left dorsal premotor cortex, but only if movements relied on internal cues. In addition, synaptic activity in the rCMA had a stronger influence on activity in the basal ganglia in the context of internally selected movements in asymptomatic carriers relative to non-carriers. We infer that this reorganization of striatocortical motor loops reflects a compensatory effort to overcome latent nigrostriatal dysfunction.
Assuntos
Córtex Motor/patologia , Doença de Parkinson/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idade de Início , Alelos , Feminino , Dedos , Genótipo , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Modelos Genéticos , Córtex Motor/fisiopatologia , Movimento/fisiologia , Mutação , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Desempenho Psicomotor/fisiologia , Tempo de ReaçãoRESUMO
Valve-sparing aortic root reconstruction is an up- and-coming approach for patients suffering from aortic valve insufficiencies which promises to significantly reduce complications. However, the success of the treatment strongly depends on the challenging task of choosing the correct size of the prosthesis, for which, up to now, surgeons solely have to rely on their experience. Here, we present a novel machine learning based approach, which might make it possible to predict the size of the prosthesis from pre-operatively acquired ultrasound images. We utilize support vector regression to train a prediction model on three geometric features extracted from the ultrasound data. In order to evaluate the accuracy and robustness of our approach we created a large data base of porcine aortic root geometries in a healthy state and an artificially dilated state. Our results indicate that prediction of correct prosthesis sizes is feasible. Furthermore, they suggest that it is crucial that the training data set faithfully represents the diversity of aortic root geometries.
Assuntos
Aorta/anatomia & histologia , Valva Aórtica/anatomia & histologia , Prótese Vascular , Próteses Valvulares Cardíacas , Desenho de Prótese , Idoso , Algoritmos , Animais , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Modelos Teóricos , Sus scrofa , UltrassomRESUMO
Hypersalivation (sialorrhea) is a common complaint of patients with neurodegenerative disorders such as Parkinson's disease or amyotrophic lateral sclerosis and a frequently disabling side effect of atypical antipsychotic drugs. Conventional treatment including oral anticholinergic or antihistamine medication is often limited by adverse effects and lack of efficacy. Over the past few years, several studies reported decreased drooling after injections of botulinum toxin into the salivary glands. This review describes the current state of treatment of sialorrhea with botulinum toxin.
Assuntos
Toxinas Botulínicas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sialorreia/tratamento farmacológico , Humanos , Resultado do TratamentoRESUMO
A novel neurological syndrome has recently been described to be associated with an expanded polyglutamine domain. The expansion results from partial duplication within the TATA-binding protein (TBP). By investigation of 604 sporadic and familial cases with various forms of neurological syndromes and 157 unaffected individuals, we found repeat expansions in the TBP in four patients of two families with autosomal dominant inheritance of ataxia, dystonia, and intellectual decline. Two different genotypes for the repetitive sequence could be demonstrated which led to elongated polyglutamine stretches between 50 and 55 residues, whereas normal alleles with 27 to a maximum of 44 glutamine residues were found in this study. The expansion to 50 or more glutamine residues results in a pathological phenotype and confirms the report of a new polyglutamine disease.