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1.
NPJ Digit Med ; 6(1): 43, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36927996

RESUMO

Ataxias are a group of movement disorders that are characterized by progressive loss of balance, impaired coordination and speech disturbance, which together lead to markedly reduced quality of life. Speech disturbance is clinically diagnosed, but methods for objective assessment of severity are lacking. Using 71 sets of speech recordings from ataxia patients, we developed an automated classification system. With a tolerance of ±1 point, this classification system correctly predicted experts' ratings of speech disturbance according to item 4 of the Scale for Assessment and rating of ataxia (SARA) in 80% of cases. We thereby demonstrate feasibility of computer-assisted voice analysis for automated assessment of severity of speech disturbance.

3.
Cerebellum ; 18(5): 873-881, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31422550

RESUMO

Sporadic adult-onset ataxia of unknown etiology (SAOA) is a non-genetic neurodegenerative disorder of the cerebellum of unknown cause which manifests with progressive ataxia without severe autonomic failure. Although SAOA is associated with cerebellar degeneration, little is known about the specific cerebellar atrophy pattern in SAOA. Thirty-seven SAOA patients and 49 healthy controls (HCs) were included at two centers. We investigated the structural and functional characteristics of SAOA brains using voxel-based morphometry (VBM) and resting-state functional imaging (rs-fMRI). In order to examine the functional consequence of structural cerebellar alterations, the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and then assessed their relation with disease severity, disease duration, and age of onset within these regions. Group differences were investigated using two-sample t tests, controlling for age, gender, site, and the total intracranial volume. The VBM analysis revealed a significant, mostly bilateral reduction of local gray matter (GM) volume in lobules I-V, V, VI, IX, X, and vermis VIII a/b in SAOA patients, compared with HCs. The GM volume loss in these regions was significantly associated with disease severity, disease duration, and age of onset. The disease-related atrophy regions did not show any functional alternations compared with HCs but were functionally characterized by high ALFF and poor DC compared with intact cerebellar regions. Our data revealed volume reduction in SAOA in cerebellar regions that are known to be involved in motor and somatosensory processing, corresponding with the clinical phenotype of SAOA. Our data suggest that the atrophy occurs in those cerebellar regions which are characterized by high ALFF and poor DC. Further studies have to show if these findings are specific for SAOA, and if they can be used to predict disease progression.


Assuntos
Atrofia/diagnóstico por imagem , Ataxia Cerebelar/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Descanso , Adulto , Idoso , Atrofia/fisiopatologia , Ataxia Cerebelar/fisiopatologia , Cerebelo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Descanso/fisiologia
4.
J Neurol ; 262(1): 54-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25287016

RESUMO

Focal lesions of brainstem, thalamus, and subcortical white matter may cause movement disorders that are clinically indistinguishable from cerebellar symptoms. It is suspected that ataxia in these cases is due to damage of efferent or afferent pathways of the cerebellum. However, the precise anatomical correlate often remains undefined. We used deterministic diffusion tensor magnetic resonance imaging (DTI) tractography to study the anatomical relationship between lesions causing ataxia and efferent cerebellar pathways. Study subjects were six male patients with focal lesions of different etiology (demyelination, hemorrhage, ischemia, neoplasm) outside the cerebellum. Five patients had cerebellar-like ataxia with prominent contralateral upper limb involvement. One patient with an almost midline mesencephalic lesion had a symmetrical ataxic syndrome. We used 3T MRI (Intera, Philips Medical Systems, Best, Netherlands) and DTI tractography (32 directions, StealthViz DTI, Medtronic Navigation, Louisville, USA) to delineate the dentato-rubro-thalamo-cortical tract (DRT). In all patients, tractography demonstrated focal lesions affecting the DRT in different locations. We conclude that in vivo mapping of cerebral pathways using DTI tractography in patients with focal extracerebellar brain lesions may provide direct evidence of circumscribed damage to the DRT, causing unilateral cerebellar-like ataxia. Also, a unilateral mesencephalic lesion at the level of the crossing of the DRT may cause bilateral ataxia.


Assuntos
Ataxia/patologia , Núcleos Cerebelares/patologia , Córtex Cerebral/patologia , Imagem de Tensor de Difusão/métodos , Tálamo/patologia , Tremor/patologia , Adolescente , Idoso , Idoso de 80 Anos ou mais , Ataxia Cerebelar/patologia , Vias Eferentes/patologia , Humanos , Masculino , Pessoa de Meia-Idade
5.
Eur J Neurol ; 21(4): 552-62, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24418350

RESUMO

BACKGROUND AND OBJECTIVES: The ataxias are a challenging group of neurological diseases due the aetiological heterogeneity and the complexity of the genetic subtypes. This guideline focuses on the heredodegenerative ataxias. The aim is to provide a peer-reviewed evidence-based guideline for clinical neurologists and other specialist physicians responsible for the care of patients with ataxia. METHODS: This guideline is based on systematic evaluations of the relevant literature and on three consensus meetings of the task force. DIAGNOSIS: If acquired causes are ruled out, and if the disease course is rather slowly progressive, a (heredo)degenerative disease is likely. A positive family history gives much guidance. In the case of a dominant family history, first line genetic screening is recommended for spinocerebellar ataxia (SCA) 1, 2, 3, 6, 7 and 17 (level B), and in Asian patients also for dentatorubral-pallidoluysian atrophy (DRPLA). In the case of recessive disease, a stepwise diagnostic work-up is recommended, including both biochemical markers and targeted genetic testing, particularly aimed at Friedreich's ataxia, ataxia telangiectasia, ataxia due to vitamin E deficiency, polymerase gamma gene (POLG gene, various mutations), autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) and ataxia with oculomotor apraxia (AOA) types 1 and 2. If family history is negative, we still advise to screen for the more common dominant and recessive ataxias. In addition, if onset is below 45 years we recommend the full work-up for recessive ataxias; if onset is above 45 years we recommend to screen for fragile X mental retardation 1 FMR1 premutations (good practice points). In sporadic cases with an onset after 30 years, a diagnosis of multiple system atrophy should be considered (good practice point). In particular the genetic work-up will change over the upcoming years due to the diagnostic utility of new techniques such as gene panel diagnostics based on next generation sequencing for routine work-up, or even whole exome and genome sequencing for selected cases. TREATMENT: Some of the rare recessive ataxias are treatable, but for most of the heredodegenerative ataxias treatment is purely symptomatic. Idebenone is not effective in Friedreich's ataxia (level A). Riluzole (level B) and amantadine (level C) might provide symptomatic relief, irrespective of exact etiology. Also, varenicline for SCA3 patients (level B) can be considered. There is level Class II evidence to recommend physiotherapy, and Class III data to support occupational therapy.


Assuntos
Ataxia/diagnóstico , Ataxia/terapia , Consenso , Guias como Assunto/normas , Ataxia/genética , Doença Crônica , Bases de Dados Factuais/estatística & dados numéricos , Humanos
6.
Cerebellum ; 13(2): 237-42, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24197754

RESUMO

Whole body vibration (WBV) is a biomechanical treatment used widely in professional sports and rehabilitation. We examined the effect of stochastic WBV on ataxia in spinocerebellar ataxia types 1, 2, 3, and 6 (SCA 1, 2, 3 and 6) in a single-center double-blind sham-controlled study. Stochastic WBV was applied on four sequent days, each treatment consisting of five stimulus trains of 60-s duration at a frequency of 6.5 Hz and 60-s resting time between stimuli (n = 17). Patients allocated to the sham group received the same treatment with 1 Hz (n = 15). All patients were rated at baseline and after the last treatment using clinical scores (SARA, SCAFI, and INAS). After treatment, we found significant improvements of gait, posture, and speed of speech in the verum group while limb kinetics and ataxia of speech did not respond. Stochastic WBV might act on proprioceptive mechanisms and could also stimulate non-cerebellar/compensatory mechanisms. But at present, the involved cellular mechanism and the presumed neuronal loops cannot be deciphered. Thus, future work is needed to understand the mechanisms of whole body vibration. Finally, the use of stochastic WBV could provide a supplementation to treat ataxia in SCA and can be combined with physiotherapeutical motor training.


Assuntos
Ataxias Espinocerebelares/terapia , Vibração/uso terapêutico , Método Duplo-Cego , Feminino , Marcha , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Postura , Índice de Gravidade de Doença , Fala , Processos Estocásticos , Resultado do Tratamento
8.
Nervenarzt ; 84(6): 709-14, 2013 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-23756819

RESUMO

BACKGROUND: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder which causes early sustained disability and quality of life impairment. Recently, a self-reported questionnaire focusing on MSA-specific symptoms (Multiple System Atrophy Quality of Life questionnaire, MSA-QoL) was developed in the English language. This article reports the validation of the German translation of the MSA-QoL. METHODS: Translation of the MSA-QoL was implemented in a 3-tiered approach including a forward translation, a back translation and an independent review. For the validation study 38 consecutive patients with MSA according to the consensus criteria were recruited by the participating centers in a German-Austrian cohort. Data were analyzed using standard psychometric procedures. RESULTS: As determined by the independent review, the German translation of the MSA-QoL was classified as fully equivalent to the English version. The validation study confirmed good psychometric properties of the rating scale. CONCLUSION: The German translation of the MSA-QoL was shown to be a reliable patient-reported rating scale to determine health-related quality of life in MSA patients.


Assuntos
Indicadores Básicos de Saúde , Atrofia de Múltiplos Sistemas/diagnóstico , Atrofia de Múltiplos Sistemas/psicologia , Psicometria/métodos , Qualidade de Vida/psicologia , Inquéritos e Questionários , Tradução , Áustria , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Nervenarzt ; 84(2): 137-42, 2013 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-23338152

RESUMO

Spinocerebellar ataxias are genetically heterogeneous autosomal dominant ataxia disorders. To date more than 30 different subtypes are known. In Germany particularly SCA1, SCA2, SCA3 and SCA6 are prevalent, as well as the less frequent subtypes SCA5, SCA14, SCA15, SCA17 and SCA28. Genetic causes range from coding repeat expansions (polyglutamine diseases), to non-coding expansions as well as conventional mutations. In some subtypes the genetic background is currently unknown. Age of onset, typical clinical findings and geographic distribution may help to reach a correct diagnosis; however a definitive diagnosis requires molecular genetic testing.


Assuntos
Ataxias Espinocerebelares/genética , Adulto , Estudos Transversais , Análise Mutacional de DNA , Alemanha , Humanos , Exame Neurológico , Peptídeos/genética , RNA não Traduzido/genética , Ataxias Espinocerebelares/classificação , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/epidemiologia , Repetições de Trinucleotídeos/genética
10.
Cerebellum ; 12(3): 418-28, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23090211

RESUMO

Although ataxia is by definition the prominent symptom of ataxia disorders, there are various neurological signs that may accompany ataxia in affected patients. Reliable and quantitative assessment of these signs is important because they contribute to disability, but may also interfere with ataxia. Therefore we devised the Inventory of Non-Ataxia Signs (INAS), a list of neurological signs that allows determining the presence and severity of non-ataxia signs in a standardized way. INAS underwent a rigorous validation procedure that involved a trial of 140 patients with spinocerebellar ataxia (SCA) for testing of inter-rater reliability and another trial of 28 SCA patients to assess short-term intra-rater reliability. In addition, data of the ongoing EUROSCA natural history study were used to determine the reproducibility, responsiveness and validity of INAS. Inter-rater reliability and short-term test-retest reliability was high, both for the total count and for most of the items. However, measures of responsiveness, such as the smallest detectable change and the clinically important change were not satisfactory. In addition, INAS did not differentiate between subjects that were subjectively stable and those that worsened in the 2-year observation period. In summary, INAS and INAS count showed good reproducibility, but unsatisfactory responsiveness. The present analysis and published data from the EUROSCA natural history study suggest that INAS is a valid measure of extracerebellar involvement in progressive ataxia disorders. As such, it is useful as a supplement to the measures of ataxia, but not as a primary outcome measure in future interventional trials.


Assuntos
Exame Neurológico , Índice de Gravidade de Doença , Ataxias Espinocerebelares/diagnóstico , Área Sob a Curva , Europa (Continente) , Feminino , Humanos , Estudos Longitudinais , Masculino , Psicometria , Reprodutibilidade dos Testes , Ataxias Espinocerebelares/classificação , Ataxias Espinocerebelares/genética , Estatística como Assunto
11.
Eur Neurol ; 69(1): 53-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23146840

RESUMO

In a previous retrospective study, we demonstrated that falls are common and often injurious in dominant spinocerebellar ataxias (SCAs) and that nonataxia features play an important role in these falls. Retrospective surveys are plagued by recall bias for the presence and details of prior falls. We therefore sought to corroborate and extend these retrospective findings by means of a prospective extension of this fall study. 113 patients with SCA1, SCA2, SCA3 or SCA6, recruited from the EuroSCA natural history study, were asked to keep a fall diary in between their annual visits to the participating centres. Additionally, patients completed a detailed questionnaire about the first three falls, to identify specific fall circumstances. Relevant disease characteristics were retrieved from the EuroSCA registry. 84.1% of patients reported at least one fall during a time period of 12 months. Fall-related injuries were common and their frequency increased with that of falls. The presence of nonataxia symptoms was associated with a higher fall frequency. This study confirms that falls are a frequent and serious complication of SCA, and that the presence of nonataxia symptoms is an important etiological factor in its occurrence.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Ataxias Espinocerebelares/complicações , Ataxias Espinocerebelares/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Ataxias Espinocerebelares/genética
12.
Clin Neuroradiol ; 22(2): 141-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21971720

RESUMO

PURPOSE: The aim of the study was to examine the effects of mechanical thrombectomy using the Solitaire stent in patients with thromboembolic occlusions of the intracranial carotid artery bifurcation (carotid T) or middle cerebral artery (MCA) and to compare the results with a historical cohort treated with local intraarterial thrombolysis using urokinase. METHODS: The time intervals from stroke onset to treatment, recanalization rates, occlusion sites, recanalization times and functional outcomes on the modified Rankin scale at 3 months in 25 patients treated with the Solitaire stent between 2010 and 2011 were evaluated. The data were compared with those of a historical cohort of 62 patients treated with local intraarterial thrombolysis between 1992 and 2001. RESULTS: A total of 15 out of 25 (60%) patients treated with mechanical thrombectomy and 25 out of 62 (40%) treated with local intraarterial thrombolysis achieved a modified Rankin score of ≤2 (p = 0.07). Occlusion sites, intervals from stroke onset to treatment and rates of parenchymal hematomas, 3 out of 25 (12%) versus 8 out of 62 (13%), were similar in both cohorts while the recanalization rate was significantly higher, 22 out of 25 (88%) versus 33 of 62 (53%), in the mechanical thrombectomy group (p ≤ 0.01). CONCLUSION: The data show that mechanical thrombectomy is superior to local intraarterial thrombolysis with respect to the recanalization rate in patients with thrombeoembolic carotid T or MCA occlusions.


Assuntos
Estenose das Carótidas/terapia , Infarto da Artéria Cerebral Média/terapia , Trombólise Mecânica/métodos , Terapia Trombolítica/métodos , Idoso , Estenose das Carótidas/diagnóstico por imagem , Fibrinolíticos/administração & dosagem , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Injeções Intra-Arteriais , Pessoa de Meia-Idade , Radiografia , Resultado do Tratamento , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem
13.
Neurology ; 77(11): 1035-41, 2011 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-21832228

RESUMO

OBJECTIVE: To obtain quantitative data on the progression of the most common spinocerebellar ataxias (SCAs) and identify factors that influence their progression, we initiated the EUROSCA natural history study, a multicentric longitudinal cohort study of 526 patients with SCA1, SCA2, SCA3, or SCA6. We report the results of the 1- and 2-year follow-up visits. METHODS: As the primary outcome measure we used the Scale for the Assessment and Rating of Ataxia (SARA, 0-40), and as a secondary measure the Inventory of Non-Ataxia Symptoms (INAS, 0-16) count. RESULTS: The annual increase of the SARA score was greatest in SCA1 (2.18 ± 0.17, mean ± SE) followed by SCA3 (1.61 ± 0.12) and SCA2 (1.40 ± 0.11). SARA progression in SCA6 was slowest and nonlinear (first year: 0.35 ± 0.34, second year: 1.44 ± 0.34). Analysis of the INAS count yielded similar results. Larger expanded repeats and earlier age at onset were associated with faster SARA progression in SCA1 and SCA2. In SCA1, repeat length of the expanded allele had a similar effect on INAS progression. In SCA3, SARA progression was influenced by the disease duration at inclusion, and INAS progression was faster in females. CONCLUSIONS: Our study gives a comprehensive quantitative account of disease progression in SCA1, SCA2, SCA3, and SCA6 and identifies factors that specifically affect disease progression.


Assuntos
Progressão da Doença , Doença de Machado-Joseph/classificação , Doença de Machado-Joseph/diagnóstico , Ataxias Espinocerebelares/classificação , Ataxias Espinocerebelares/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Doença de Machado-Joseph/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Ataxias Espinocerebelares/epidemiologia , Adulto Jovem
14.
Nervenarzt ; 82(8): 994-1001, 2011 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-21789693

RESUMO

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/genética
15.
Parkinsonism Relat Disord ; 16(6): 381-3, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20434388

RESUMO

A common subset of genetic risk factors for Parkinson's disease (PD) and essential tremor (ET) has been postulated. Recently, an association between the dopamine D(3) receptor (DRD3) Ser9Gly polymorphism and ET has been reported. We studied whether PD tremor is influenced by Ser9Gly in a genetic association study based on the gene bank of the German Competence Network on Parkinson's disease. The study included analyses of motor predominance (mixed, hypokinetic, and tremor), and tremor type (resting, postural, and action). We did not identify any effect of DRD3 Ser9Gly on tremor in PD, even when regarding various symptom combinations to avoid missing a weak effect on the phenotype. Additional studies incorporating symptoms at disease onset, and grading of tremor response to dopaminergic therapy, are warranted.


Assuntos
Predisposição Genética para Doença/genética , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D3/genética , Tremor/genética , Idoso , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Fenótipo
16.
Neurology ; 74(8): 678-84, 2010 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-20177122

RESUMO

OBJECTIVE: To determine the longitudinal metric properties of recently developed clinical assessment tools in spinocerebellar ataxia (SCA). METHODS: A subset of 171 patients from the EUROSCA natural history study cohort (43 SCA1, 61 SCA2, 37 SCA3, and 30 SCA6) were examined after 1 year of follow-up. Score changes and effect size indices were calculated for clinical scales (Scale for the Assessment and Rating of Ataxia [SARA], Inventory of Non-Ataxia Symptoms [INAS]), functional tests (SCA Functional Index [SCAFI] and components), and a patient-based scale for subjective health status (EQ-5D visual analogue scale [EQVAS]). Responsiveness was determined in relation to the patient's global impression (PGI) of change and reproducibility described as retest reliability for the stable groups and smallest detectable change. RESULTS: Within the 1-year follow-up period, SARA, INAS, and SCAFI but not EQVAS indicated worsening in the whole group and in the groups with subjective (PGI) worsening. SCAFI and its 9-hole pegboard (9HPT) component also deteriorated in the stable groups. Standardized response means were highest for 9HPT (-0.67), SARA (0.50), and SCAFI (-0.48) with accordingly lower sample size estimates of 143, 250, or 275 per group for a 2-arm interventional trial that aims to reduce disease progression by 50%. SARA and EQVAS performed best to distinguish groups classified as worse by PGI. All scales except EQVAS reached the criterion for retest reliability. CONCLUSION: While both the Scale for the Assessment and Rating of Ataxia and the SCA Functional Index (SCAFI) (and its 9-hole pegboard component) had favorable measurement precision, the clinical relevance of SCAFI and 9-hole pegboard score changes warrants further exploration. The EQ-5D visual analogue scale proved insufficient for longitudinal assessment, but validly reflected patients' impression of change.


Assuntos
Índice de Gravidade de Doença , Ataxias Espinocerebelares/diagnóstico , Área Sob a Curva , Progressão da Doença , Nível de Saúde , Humanos , Seleção de Pacientes , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários
17.
Neurosci Lett ; 468(3): 183-5, 2010 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-19854238

RESUMO

Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease of the central nervous system. We investigated the association of two missense variants of the MTHFR gene, i.e. MTHFR c.677C>T (p.A222V) and c.1298A>C (p.E429A), in 138 patients with clinically definite multiple sclerosis of relapsing-remitting course and 138 age- and gender-matched healthy controls. No significant differences were found in the frequency of the MTHFR c.677C>T polymorphism between MS patients and healthy controls. However, the genotype frequencies of the missense variant MTHFR c.1298A>C were significantly different between patients (AA/AC/CC: 0.34/0.55/0.11) and controls (0.52/0.36/0.12; Pearson's chi(2)=11.1; p=0.004). These results suggest that homozygosity for the A allele of MTHFR c.1298A>C may be protective against the incidence of MS. If confirmed in an independent study sample, the underlying mechanisms should be investigated, which may lead to novel insights in biochemical factors influencing the aetiology and pathophysiology of MS.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Esclerose Múltipla Recidivante-Remitente/genética , Adulto , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Mutação de Sentido Incorreto
18.
Clin Neurophysiol ; 120(3): 632-5, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19201647

RESUMO

OBJECTIVE: A characteristic feature of spinocerebellar ataxia type 2 (SCA2) is saccadic slowing at early disease stages. We sought to determine whether this sign is detectable before clinical manifestation and quantifies the disease progression throughout life in linear fashion. METHODS: In a specialized ataxia clinic, 54 presymptomatic carriers of SCA2 polyglutamine expansions and 56 relatives without mutation were documented with regard to their maximal saccade velocity (MSV). RESULTS: Among the control individuals, a significant effect of aging on MSV was observed. After elimination of this age influence through a matched-pair approach, a presymptomatic decrease of MSV could be shown. The MSV reduction was stronger in carriers of large expansions. In the years before calculated disease manifestation, the MSV impairment advanced insidiously. CONCLUSION: Saccade velocity is a sensitive SCA2 endophenotype that reflects early pontine degeneration and may be a useful diagnostic parameter before the onset of ataxia. SIGNIFICANCE: Future neuroprotective therapies of polyglutamine neurodegeneration may be assessed by MSV from earliest to prefinal disease stages.


Assuntos
Transtornos da Motilidade Ocular/etiologia , Transtornos da Motilidade Ocular/fisiopatologia , Músculos Oculomotores/fisiopatologia , Movimentos Sacádicos/fisiologia , Ataxias Espinocerebelares/complicações , Ataxias Espinocerebelares/fisiopatologia , Adolescente , Adulto , Idoso , Ataxinas , Cerebelo/fisiopatologia , Progressão da Doença , Diagnóstico Precoce , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Vias Neurais/fisiopatologia , Transtornos da Motilidade Ocular/diagnóstico , Músculos Oculomotores/inervação , Valor Preditivo dos Testes , Prognóstico , Ataxias Espinocerebelares/diagnóstico , Adulto Jovem
19.
J Neurol Neurosurg Psychiatry ; 79(12): 1408-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19010954

RESUMO

Spinal dural arteriovenous fistulae (SDAVF) are acquired spinal vascular malformations, in which a small connection between a radicular artery and radicular vein causes venous hypertension, congestive myelopathy and infarction of the spinal cord. Here the case of a 47-year-old man is presented who had pain in his back irradiating to his right leg, numbness of his right leg as well as weakness of both legs. Urination was disturbed with detection of residual urine. Six weeks later he developed a progressive paraparesis of the legs. A T2 weighted MRI of the lower back showed intramedullary hyperintensity. A myelitis was assumed and treatment with acyclovir and dexamethasone was started. Nevertheless, he developed total paralysis of his legs. Six years later, re-evaluation of the initial MRI and a new MRI showed abnormal blood vessels on the dorsal side of the spinal cord, which had been overlooked at the first MRI examination. Spinal angiography demonstrated an arteriovenous fistula. Fistula obliteration was performed. Six months later he was able to stand with canes for 2 min and showed improvement in sensibility. The remarkable aspect of this case of SDAVF is the relevant improvement of complete paraplegia by surgical obliteration 78 months after onset of symptoms. The delay of more than 6 years between onset of first symptoms and final diagnosis underlines the difficulties in making a correct diagnosis of SDAVF. However, even after delayed diagnosis, surgical obliteration should be done, as improvement of neurological function can still be achieved.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/diagnóstico , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Paraplegia/terapia , Coluna Vertebral/patologia , Aciclovir/farmacologia , Malformações Arteriovenosas/patologia , Malformações Arteriovenosas/terapia , Dexametasona/farmacologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mielite/tratamento farmacológico , Paraparesia/patologia , Medula Espinal/patologia , Fatores de Tempo , Resultado do Tratamento
20.
Neurology ; 71(9): 670-6, 2008 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-18725592

RESUMO

BACKGROUND: A consensus conference on multiple system atrophy (MSA) in 1998 established criteria for diagnosis that have been accepted widely. Since then, clinical, laboratory, neuropathologic, and imaging studies have advanced the field, requiring a fresh evaluation of diagnostic criteria. We held a second consensus conference in 2007 and present the results here. METHODS: Experts in the clinical, neuropathologic, and imaging aspects of MSA were invited to participate in a 2-day consensus conference. Participants were divided into five groups, consisting of specialists in the parkinsonian, cerebellar, autonomic, neuropathologic, and imaging aspects of the disorder. Each group independently wrote diagnostic criteria for its area of expertise in advance of the meeting. These criteria were discussed and reconciled during the meeting using consensus methodology. RESULTS: The new criteria retain the diagnostic categories of MSA with predominant parkinsonism and MSA with predominant cerebellar ataxia to designate the predominant motor features and also retain the designations of definite, probable, and possible MSA. Definite MSA requires neuropathologic demonstration of CNS alpha-synuclein-positive glial cytoplasmic inclusions with neurodegenerative changes in striatonigral or olivopontocerebellar structures. Probable MSA requires a sporadic, progressive adult-onset disorder including rigorously defined autonomic failure and poorly levodopa-responsive parkinsonism or cerebellar ataxia. Possible MSA requires a sporadic, progressive adult-onset disease including parkinsonism or cerebellar ataxia and at least one feature suggesting autonomic dysfunction plus one other feature that may be a clinical or a neuroimaging abnormality. CONCLUSIONS: These new criteria have simplified the previous criteria, have incorporated current knowledge, and are expected to enhance future assessments of the disease.


Assuntos
Doenças do Sistema Nervoso Autônomo/diagnóstico , Encéfalo/patologia , Ataxia Cerebelar/diagnóstico , Atrofia de Múltiplos Sistemas/diagnóstico , Transtornos Parkinsonianos/diagnóstico , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Gânglios da Base/patologia , Gânglios da Base/fisiopatologia , Encéfalo/fisiopatologia , Ataxia Cerebelar/fisiopatologia , Cerebelo/patologia , Cerebelo/fisiopatologia , Diagnóstico Diferencial , Corpos de Inclusão/metabolismo , Corpos de Inclusão/patologia , Atrofia de Múltiplos Sistemas/fisiopatologia , Transtornos Parkinsonianos/fisiopatologia , alfa-Sinucleína/metabolismo
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