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OBJECTIVE: Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment. METHODS: This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (>median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing. RESULTS: All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation. INTERPRETATION: Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024;95:886-897.
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Anticoagulantes , Aspirina , Dissecação da Artéria Vertebral , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Dissecação da Artéria Vertebral/tratamento farmacológico , Dissecação da Artéria Vertebral/diagnóstico por imagem , Dissecação da Artéria Vertebral/complicações , Aspirina/uso terapêutico , Anticoagulantes/uso terapêutico , Adulto , Fibrinolíticos/uso terapêutico , Idoso , Resultado do TratamentoRESUMO
BACKGROUND: Despite evolving treatments, functional recovery in patients with large vessel occlusion stroke remains variable and outcome prediction challenging. Can we improve estimation of functional outcome with interpretable deep learning models using clinical and magnetic resonance imaging data? METHODS: In this observational study, we collected data of 222 patients with middle cerebral artery M1 segment occlusion who received mechanical thrombectomy. In a 5-fold cross validation, we evaluated interpretable deep learning models for predicting functional outcome in terms of modified Rankin scale at 3 months using clinical variables, diffusion weighted imaging and perfusion weighted imaging, and a combination thereof. Based on 50 test patients, we compared model performances to those of 5 experienced stroke neurologists. Prediction performance for ordinal (modified Rankin scale score, 0-6) and binary (modified Rankin scale score, 0-2 versus 3-6) functional outcome was assessed using discrimination and calibration measures like area under the receiver operating characteristic curve and accuracy (percentage of correctly classified patients). RESULTS: In the cross validation, the model based on clinical variables and diffusion weighted imaging achieved the highest binary prediction performance (area under the receiver operating characteristic curve, 0.766 [0.727-0.803]). Performance of models using clinical variables or diffusion weighted imaging only was lower. Adding perfusion weighted imaging did not improve outcome prediction. On the test set of 50 patients, binary prediction performance between model (accuracy, 60% [55.4%-64.4%]) and neurologists (accuracy, 60% [55.8%-64.21%]) was similar when using clinical data. However, models significantly outperformed neurologists when imaging data were provided, alone or in combination with clinical variables (accuracy, 72% [67.8%-76%] versus 64% [59.8%-68.4%] with clinical and imaging data). Prediction performance of neurologists with comparable experience varied strongly. CONCLUSIONS: We hypothesize that early prediction of functional outcome in large vessel occlusion stroke patients may be significantly improved if neurologists are supported by interpretable deep learning models.
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Isquemia Encefálica , Aprendizado Profundo , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Neurologistas , Trombectomia/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Prognóstico , Resultado do Tratamento , Estudos Retrospectivos , Isquemia Encefálica/terapiaRESUMO
BACKGROUND AND PURPOSE: Mechanical thrombectomy is less effective in patients aged 80 years or older. Our goal was to better understand the impact of age in general on recanalization rates and clinical outcome. METHODS: We performed a retrospective analysis of our prospective database of adult patients with acute ischemic stroke due to large vessel occlusions, who had undergone mechanical thrombectomy between 2019 and mid-2021. The cohort was categorized into five age groups: 18 - 49, 50 - 59, 60 - 69, 70 - 79 and ≥ 80 years. Our primary outcome measure was clinical outcome at three months after mechanical thrombectomy, measured by the mRS score. Secondary outcomes were procedure times and rates of successful recanalization, defined by mTICI ≥ 2b. RESULTS: Data of 264 patients were analyzed. There were no significant differences in procedure times (p = 0.46) or in rates of successful recanalization (p = 0.49) between age groups. There was a significant association of age and mRS score at three months (p < 0.0001): From youngest to oldest group, odds of functional independence (mRS ≤ 2) decreased (80.0% vs. 21.3%) and odds of death (mRS 6) increased (13.3% vs. 57.3%). Increasing age was significantly associated with lower rates of functional independence (OR 0.93; [95% CI 0.90 - 0.95]), higher rates of care dependency (OR 1.04; [95% CI 1.01 - 1.07]) and higher mortality rates (OR 1.06; [95% CI 1.04 - 1.09]). CONCLUSION: Higher age had no significant impact on recanalization times or recanalization rates but was strongly associated with worse clinical outcome after mechanical thrombectomy.
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OBJECTIVES: Intracranial atherosclerotic disease (ICAD) is a major cause of large vessel occlusion (LVO) in acute ischemic stroke (AIS). Our study aimed to analyze the effect of percutaneous transluminal angioplasty and stenting (PTAS) in patients with ICAD undergoing rescue treatment in terms of functional outcome and mortality rate at 90 days and compare the results to LVO with thromboembolic origins. MATERIALS AND METHODS: A retrospective review of a mechanical thrombectomy (MT) single center database from 01/2019 to 09/2021 was carried out using chart review and angiogram analysis. From 469 acute stroke patients, 361 patients were enroled in the study, of whom twenty-four (6.6%) were diagnosed with underlying ICAD and treated with angioplasty and stent reconstruction (PTAS) with a standardized medication protocol. Successful reperfusion, peri-procedural complications, and functional independence at 90 days were collected as outcomes. RESULTS: There was no difference in age or admission National Institutes of Health Stroke Scale (NIHSS). Onset to groin puncture (median 460 vs 277 min, P = 0.019) was significantly longer in the ICAD group. The procedure time (median 73 vs 60 min, P = 0.137) did not differ. Successful reperfusion was achieved in 95.8% of ICAD and 91.1% of the remaining patients (P = 0.445). Functional independence (mRS ≤ 2) at 90 days was achieved in 45.8% (11/24) and 42.7% (144/337, (P = 0.767)). The mortality rates (mRS 6) at 90 days were similar (29.2% vs 29.4% (P = 0.983)). CONCLUSION: Despite significantly longer treatment delays, the outcome and revascularization rates of ICAD patients were similar to the thromboembolic cohort. Our proposed protocol of PTAS and medication protocol in ICAD was effective with a similar safety profile as MT in general.
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Arteriosclerose Intracraniana , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/terapia , Resultado do Tratamento , Trombectomia/efeitos adversos , Trombectomia/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Estudos Retrospectivos , Stents , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/terapiaRESUMO
BACKGROUND AND PURPOSE: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. METHODS: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. RESULTS: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. CONCLUSIONS: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.
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COVID-19/diagnóstico por imagem , Artérias Cerebrais/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Transtornos Cerebrovasculares/diagnóstico por imagem , AVC Isquêmico/diagnóstico por imagem , Idoso , Anticorpos Antivirais/líquido cefalorraquidiano , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , COVID-19/líquido cefalorraquidiano , COVID-19/complicações , COVID-19/fisiopatologia , Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19 , Hemorragia Cerebral/etiologia , Líquido Cefalorraquidiano/imunologia , Líquido Cefalorraquidiano/virologia , Transtornos Cerebrovasculares/líquido cefalorraquidiano , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Transtornos da Consciência/etiologia , Transtornos da Consciência/fisiopatologia , Meios de Contraste , Estado Terminal , Eletroencefalografia , Feminino , Humanos , AVC Isquêmico/etiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Índice de Gravidade de Doença , Suíça , Centros de Atenção Terciária , Tomografia Computadorizada por Raios XRESUMO
See Klockgether (doi:10.1093/awv253) for a scientific commentary on this article.The spinocerebellar ataxias types 2 (SCA2) and 3 (SCA3) are autosomal dominantly inherited cerebellar ataxias which are caused by CAG trinucleotide repeat expansions in the coding regions of the disease-specific genes. Although previous post-mortem studies repeatedly revealed a consistent neurodegeneration of the dopaminergic substantia nigra in patients with SCA2 and with SCA3, parkinsonian motor features evolve only rarely. As the pathophysiological mechanism how SCA2 and SCA3 patients do not exhibit parkinsonism is still enigmatic, we performed a positron emission tomography and a post-mortem study of two independent cohorts of SCA2 and SCA3 patients with and without parkinsonian features. Positron emission tomography revealed a significant reduction of dopamine transporter levels in the striatum as well as largely unaffected postsynaptic striatal D2 receptors. In spite of this remarkable pathology in the motor mesostriatal pathway, only 4 of 19 SCA2 and SCA3 patients suffered from parkinsonism. The post-mortem investigation revealed, in addition to an extensive neuronal loss in the dopaminergic substantia nigra of all patients with spinocerebellar ataxia, a consistent affection of the thalamic ventral anterior and ventral lateral nuclei, the pallidum and the cholinergic pedunculopontine nucleus. With the exception of a single patient with SCA3 who suffered from parkinsonian motor features during his lifetime, the subthalamic nucleus underwent severe neuronal loss, which was clearly more severe in its motor territory than in its limbic or associative territories. Our observation that lesions of the motor territory of the subthalamic nucleus were consistently associated with the prevention of parkinsonism in our SCA2 and SCA3 patients matches the clinical experience that selective targeting of the motor territory of the subthalamic nucleus by focal lesions or deep brain stimulation can ameliorate parkinsonian motor features and is likely to counteract the manifestation of parkinsonism in SCA2 and SCA3 despite a severe neurodegeneration of the dopaminergic substantia nigra.
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Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Neurônios Dopaminérgicos/diagnóstico por imagem , Doença de Machado-Joseph/diagnóstico por imagem , Neostriado/diagnóstico por imagem , Transtornos Parkinsonianos/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Ataxina-2/genética , Ataxina-3/genética , Estudos de Casos e Controles , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Feminino , Humanos , Doença de Machado-Joseph/complicações , Doença de Machado-Joseph/genética , Doença de Machado-Joseph/patologia , Masculino , Pessoa de Meia-Idade , Neostriado/metabolismo , Neostriado/patologia , Doença de Parkinson/diagnóstico por imagem , Transtornos Parkinsonianos/complicações , Tomografia por Emissão de Pósitrons , Proteínas Repressoras/genética , Ataxias Espinocerebelares/complicações , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/patologia , Substância Negra/metabolismo , Substância Negra/patologia , Expansão das Repetições de Trinucleotídeos , Adulto JovemRESUMO
INTRODUCTION: A significant number of patients who present with mild symptoms following large-vessel occlusion acute ischemic stroke (LVO-AIS) are currently considered ineligible for EVT. However, they frequently experience neurological deterioration during hospitalization. This study aimed to investigate the association between neurological deterioration and hemodynamic impairment by assessing steal phenomenon derived from blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) in this specific patient cohort. PATIENTS AND METHODS: From the database of our single-center BOLD-CVR observational cohort study (June 2015-October 2023) we retrospectively identified acute ischemic stroke patients with admission NIHSS < 6, a newly detected large vessel occlusion of the anterior circulation and ineligible for EVT. Neurological deterioration during hospitalization as well as outcome at hospital discharge were rated with NIHSS score. We analyzed the association between these two outcomes and BOLD-CVR-derived steal phenomenon volume through regression analysis. Additionally, we investigated the discriminatory accuracy of steal phenomenon volume for predicting neurological deterioration. RESULTS: Forty patients were included in the final analysis. Neurological deterioration occurred in 35% of patients. In the regression analysis, a strong association between steal phenomenon volume and neurological deterioration (OR 4.80, 95% CI 1.32-31.04, p = 0.04) as well as poorer NIHSS score at hospital discharge (OR 3.73, 95% CI 1.52-10.78, p = 0.007) was found. The discriminatory accuracy of steal phenomenon for neurological deterioration prediction had an AUC of 0.791 (95% CI 0.653-0.930). DISCUSSION: Based on our results we may distinguish two groups of patients with minor stroke currently ineligible for EVT, however, showing hemodynamic impairment and exhibiting neurological deterioration during hospitalization: (1) patients exhibiting steal phenomenon on BOLD-CVR imaging as well as hemodynamic impairment on resting perfusion imaging; (2) patients exhibiting steal phenomenon on BOLD-CVR imaging, however, no relevant hemodynamic impairment on resting perfusion imaging. CONCLUSION: The presence of BOLD-CVR derived steal phenomenon may aid to further study hemodynamic impairment in patients with minor LVO-AIS not eligible for EVT.
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Learning efficacy depends on its emotional context. The contents learned and the feedback received during training tinges this context. The objective here was to investigate the influence of content and feedback on the efficacy of implicit learning and to explore using functional imaging how these factors are processed in the brain. Twenty-one participants completed 150 trials of a probabilistic classification task (predicting sun or rain based on combinations of playing cards). Smileys or frowneys were presented as feedback. In 10 of these subjects, the task was performed during functional magnetic resonance imaging. Card combinations predicting sun were remembered better than those predicting rain. Similarly, positive feedback fortified learning more than negative feedback. The presentation of smileys recruited bilateral nucleus accumbens, sensorimotor cortex, and posterior cingulum more than negative feedback did. The higher the predictive value of a card combination, the more activation was found in the lateral cerebellum. Both context and feedback influence implicit classification learning. Similar to motor skill acquisition, positive feedback during classification learning is processed in part within the sensorimotor cortex, potentially reflecting the activation of a dopaminergic projection to motor cortex (Hosp et al., 2011). Activation of the lateral cerebellum during learning of combinations with high predictive value may reflect the formation of an internal model.
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Encéfalo/fisiologia , Aprendizagem/fisiologia , Imageamento por Ressonância Magnética , Recompensa , Adulto , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico/métodos , Cerebelo/fisiologia , Dopamina/fisiologia , Retroalimentação Psicológica/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiologia , Núcleo Accumbens/fisiologia , Valor Preditivo dos Testes , Córtex Somatossensorial/fisiologiaRESUMO
Bleeding and thromboembolic (TE) complications in neurosurgical diseases have a detrimental impact on clinical outcomes. The aim of this study is to provide a scoping review of the available literature and address challenges and knowledge gaps in the management of coagulation disorders in neurosurgical diseases. Additionally, we introduce a novel research project that seeks to reduce coagulation disorder-associated complications in neurosurgical patients. The risk of bleeding after elective craniotomy is about 3%, and higher (14-33%) in other indications, such as trauma and intracranial hemorrhage. In spinal surgery, the incidence of postoperative clinically relevant bleeding is approximately 0.5-1.4%. The risk for TE complications in intracranial pathologies ranges from 3 to 20%, whereas in spinal surgery it is around 7%. These findings highlight a relevant problem in neurosurgical diseases and current guidelines do not adequately address individual circumstances. The multidisciplinary COagulation MAnagement in Neurosurgical Diseases (COMAND) project has been developed to tackle this challenge by devising an individualized coagulation management strategy for patients with neurosurgical diseases. Importantly, this project is designed to ensure that these management strategies can be readily implemented into healthcare practices of different types and with sustainable integration.
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Background: Autoregulation of the cerebral vasculature keeps brain perfusion stable over a range of systemic mean arterial pressures to ensure brain functioning, e.g., in different body positions. Verticalization, i.e., transfer from lying (0°) to upright (70°), which causes systemic blood pressure drop, would otherwise dramatically lower cerebral perfusion pressure inducing fainting. Understanding cerebral autoregulation is therefore a prerequisite to safe mobilization of patients in therapy. Aim: We measured the impact of verticalization on cerebral blood flow velocity (CBFV) and systemic blood pressure (BP), heart rate (HR) and oxygen saturation in healthy individuals. Methods: We measured CBFV in the middle cerebral artery (MCA) of the dominant hemisphere in 20 subjects using continuous transcranial doppler ultrasound (TCD). Subjects were verticalized at 0°, -5°, 15°, 30°, 45° and 70° for 3-5 min each, using a standardized Sara Combilizer chair. In addition, blood pressure, heart rate and oxygen saturation were continuously monitored. Results: We show that CBFV progressively decreases in the MCA with increasing degrees of verticalization. Systolic and diastolic BP, as well as HR, show a compensatory increase during verticalization. Conclusion: In healthy adults CBFV changes rapidly with changing levels of verticalization. The changes in the circulatory parameters are similar to results regarding classic orthostasis. Registration: ClinicalTrials.gov, identifier: NCT04573114.
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To assess the clinical spectrum of ataxia and cerebellar oculomotor deficits in the most common spinocerebellar ataxias (SCAs), we analysed the baseline data of the EUROSCA natural history study, a multicentric cohort study of 526 patients with either spinocerebellar ataxia type 1, 2, 3 or 6. To quantify ataxia symptoms, we used the Scale for the Assessment and Rating of Ataxia (SARA). The presence of cerebellar oculomotor signs was assessed using the Inventory of Non-Ataxia Symptoms (INAS). In a subgroup of patients, in which magnetic resonance images (MRIs) were available, we correlated MRI morphometric measures with clinical signs on an exploratory basis. The SARA subscores posture and gait (items 1-3), speech (item 4) and the limb kinetic subscore (items 5-8) did not differ between the genotypes. The scores of SARA item 3 (sitting), 5 (finger chase) and 6 (nose-finger test) differed between the subtypes whereas the scores of the remaining items were not different. In SCA1, ataxia symptoms were correlated with brainstem atrophy and in SCA3 with both brainstem and cerebellar atrophy. Cerebellar oculomotor deficits were most frequent in SCA6 followed by SCA3, whereas these abnormalities were less frequent in SCA1 and SCA2. Our data suggest that vestibulocerebellar, spinocerebellar and pontocerebellar circuits in SCA1, SCA2, SCA3 and SCA6 are functionally impaired to almost the same degree, but at different anatomical levels. The seemingly low prevalence of cerebellar oculomotor deficits in SCA1 and SCA2 is most probably related to the defective saccadic system in these disorders.
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Tronco Encefálico/patologia , Cerebelo/patologia , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ataxia/diagnóstico , Ataxia/patologia , Atrofia , Estudos de Coortes , Feminino , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Autonomic dysfunction has been frequently demonstrated in patients with extrapyramidal diseases by cardiovascular autonomic testing. In addition to classical testing, we applied the more detailed baroreflex and spectral analysis on three traditional cardiovascular tests in this study to get additional information on autonomic outflow. We recorded continuously blood pressure, electrocardiogram, and respiration in 35 patients with multiple system atrophy, 32 patients with progressive supranuclear palsy, 46 patients with idiopathic Parkinson's disease and in 27 corresponding healthy subjects during cardiovascular autonomic testing (metronomic breathing, Valsalva manoeuvre, head-up tilt). Baroreflex and spectral analyses were performed by using trigonometric regressive spectral analysis between and during the manoeuvres. Consistent with previous interpretations, our data showed an increase of sympathetic activity in head-up tilt and Valsalva test in healthy controls. This sympathetic activity was significantly decreased in patients with typical and atypical Parkinson syndromes. Significant modulation of baroreflex activity could be observed especially during metronomic breathing; again it was significantly lower in all patient groups. Baroreflex and spectral parameters could not only differentiate between patients and healthy controls, but also differentiate between clinically symptomatic (with autonomic dysfunction as eg. orthostatic hypotension) and asymptomatic patients. In conclusion, our approach allows the evaluation of autonomic variability during short and nonstationary periods of time and may constitute a useful advance in the assessment of autonomic function in both physiological and pathological conditions.
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Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/etiologia , Barorreflexo/fisiologia , Doenças dos Gânglios da Base/complicações , Análise Espectral/métodos , Idoso , Doenças dos Gânglios da Base/classificação , Preservação de Sangue/métodos , Eletrocardiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Respiratórios/diagnóstico , Transtornos Respiratórios/etiologia , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Manobra de Valsalva/fisiologiaRESUMO
Patient-based measures of subjective health status are increasingly used as outcome measures in interventional trials. We aimed to determine the variability and predictors of subjective health ratings in a possible target group for future interventions: the spinocerebellar ataxias (SCAs). A consecutive sample of 526 patients with otherwise unexplained progressive ataxia and genetic diagnoses of SCA1 (117), SCA2 (163), SCA3 (139), and SCA6 (107) were enrolled at 18 European referral centers. Subjective health status was assessed with a generic measure of health related quality of life, the EQ-5D (Euroqol) questionnaire. In addition, we performed a neurological examination and a screening questionnaire for affective disorders (patient health questionnaire). Patient-reported health status was compromised in patients of all genotypes (EQ-5D visual analogue scale (EQ-VAS) mean 61.45 +/- 20.8). Specifically, problems were reported in the dimensions of mobility (86.9% of patients), usual activities (68%), pain/discomfort (49.4%), depression/anxiety (46.4%), and self care (38.2%). Multivariate analysis revealed three independent predictors of subjective health status: ataxia severity, extent of noncerebellar involvement, and the presence of depressive syndrome. This model explained 30.5% of EQ-VAS variance in the whole sample and might be extrapolated to other SCA genotypes.
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Emoções/fisiologia , Nível de Saúde , Qualidade de Vida , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/psicologia , Adulto , Idoso , Ansiedade/diagnóstico , Ansiedade/etiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Medição da Dor , Índice de Gravidade de Doença , Ataxias Espinocerebelares/classificação , Ataxias Espinocerebelares/complicações , Estatísticas não Paramétricas , Inquéritos e QuestionáriosRESUMO
To investigate the frequency, details, and consequences of falls in patients with autosomal dominant spinocerebellar ataxias (SCAs) and to derive specific disease-related risk factors that are associated with an increased fall frequency. Two hundred twenty-eight patients with SCA1, SCA2, SCA3, or SCA6, recruited from the EuroSCA natural history study, completed a fall questionnaire that assessed the frequency, consequences, and several details of falls in the previous 12 months. Relevant disease characteristics were retrieved from the EuroSCA registry. The database of the natural history study provided the ataxia severity scores as well as the number and nature of non-ataxia symptoms. Patients (73.6%) reported at least one fall in the preceding 12 months. There was a high rate of fall-related injuries (74%). Factors that were associated with a higher fall frequency included: disease duration, severity of ataxia, the presence of pyramidal symptoms, the total number of non-ataxia symptoms, and the genotype SCA3. Factors associated with a lower fall frequency were: the presence of extrapyramidal symptoms (more specifically dystonia of the lower limbs) and the genotype SCA2. The total number of non-ataxia symptoms and longer disease duration were independently associated with a higher fall frequency in a logistic regression analysis, while the presence of extrapyramidal symptoms was independently associated with a lower fall frequency. Our findings indicate that, in addition to more obvious factors that are associated with frequent falls, such as disease duration and ataxia severity, non-ataxia manifestations in SCA play a major role in the fall etiology of these patients.
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Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/prevenção & controle , Adulto , Idoso , Europa (Continente)/epidemiologia , Feminino , Genótipo , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/fisiopatologia , Inquéritos e QuestionáriosRESUMO
Differential diagnosis of parkinsonian syndromes is a major challenge in movement disorders. Dysautonomia is a common feature but may vary in clinical severity and onset. The study attempted to find a pattern of autonomic abnormalities discriminative for patients with different parkinsonian syndromes. The cross-sectional study included 38 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 26 patients with idiopathic Parkinson's disease (IPD) and 27 age-matched healthy controls. Autonomic symptoms were evaluated by a standardized questionnaire. The performance of patients and controls was compared on five autonomic function tests: deep breathing, Valsalva manoeuvre, tilt-table testing, sympathetic skin response, pupillography, and 24-h ambulatory blood pressure monitoring (ABPM). Disease severity was significantly lower in IPD than PSP and MSA. Except for pupillography, none of the laboratory autonomic tests distinguished one patient group from the other alone or in combination. The same was observed on the questionnaire. Receiver operating characteristic curve revealed discriminating performance of pupil diameter in darkness and nocturnal blood pressure change. The composite score of urogenital and vasomotor domains significantly distinguished MSA from IPD patients but not from PSP. Our study supports the observation that even mild IPD is frequently indistinguishable from more severe MSA and PSP. Thus, clinical combination of motor and non-motor symptoms does not exclusively point at MSA. Pupillography, ABPM and the questionnaire may assist in delineating the three syndromes when applied in combination.
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Atrofia de Múltiplos Sistemas/diagnóstico , Doença de Parkinson/diagnóstico , Disautonomias Primárias/diagnóstico , Paralisia Supranuclear Progressiva/diagnóstico , Idoso , Monitorização Ambulatorial da Pressão Arterial , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/fisiopatologia , Doença de Parkinson/fisiopatologia , Disautonomias Primárias/fisiopatologia , Curva ROC , Reflexo Pupilar/fisiologia , Índice de Gravidade de Doença , Fenômenos Fisiológicos da Pele , Paralisia Supranuclear Progressiva/fisiopatologia , Inquéritos e QuestionáriosRESUMO
Cardiovascular autonomic dysfunction has frequently been reported in some patients with extrapyramidal syndromes, especially multiple system atrophy (MSA) but also Parkinson's disease (PD). However, there are only few reports on the prevalence of cardiovascular autonomic dysfunction progressive in supranuclear palsy (PSP). Moreover, the relation of detailed cardiovascular testing and easy to assess 24-hour ambulatory blood pressure (BP) is not known. Our study evaluates 24-hour ambulatory BP monitoring in patients with PD, PSP, MSA, and corresponding controls (Con) and relates the findings to the results of comprehensive cardiovascular autonomic testing. Twenty-three patients with PD, 25 patients with PSP, 25 patients with MSA, and 26 corresponding controls were studied by 24-hour ambulatory BP monitoring (ABPM) in comparison to cardiovascular autonomic testing. Patients with PD, PSP, and MSA presented frequently with a pathological nocturnal BP regulation (no decrease or even an increase of nocturnal BP) in comparison to the control group (PD 48%, PSP 40%, MSA 68% vs. Con 8%). In MSA and PD patients, the frequent pathological BP increase during night was closely correlated to orthostatic hypotension. Since loss of nocturnal BP fall is frequent in patients with extrapyramidal syndromes, even if they are free of subjective autonomic dysfunction, we recommend 24-hour ABPM as an easy to perform screening test, especially if detailed autonomic testing is not available. Pathological loss of nocturnal BP fall may account for increased cardiovascular mortality in extrapyramidal syndromes.
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Doenças dos Gânglios da Base/fisiopatologia , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Idoso , Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Monitorização Ambulatorial da Pressão Arterial , Estudos Transversais , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/tratamento farmacológico , Atrofia de Múltiplos Sistemas/fisiopatologia , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Paralisia Supranuclear Progressiva/complicações , Paralisia Supranuclear Progressiva/tratamento farmacológico , Paralisia Supranuclear Progressiva/fisiopatologia , Teste da Mesa InclinadaRESUMO
Multiple system atrophy (MSA) can clinically be divided into the cerebellar (MSA-C) and the parkinsonian (MSA-P) variant. However, till now, it is unknown whether autonomic dysfunction in these two entities differs regarding severity and profile. We compared the pattern of autonomic dysfunction in 12 patients with MSA-C and 26 with MSA-P in comparison with 27 age- and sex-matched healthy controls using a standard battery of autonomic function tests and a structured anamnesis of the autonomic nervous system. MSA-P patients complained significantly more often about the symptoms of autonomic dysfunctions than MSA-C patients, especially regarding vasomotor, secretomotor, and gastrointestinal subsystems. However, regarding cardiovascular, sudomotor pupil, urogenital, and sleep subsystems, there were no significant quantitative or qualitative differences as analyzed by autonomic anamnesis and testing. Our results suggest that there are only minor differences in the pattern of autonomic dysfunction between the two clinical MSA phenotypes.
Assuntos
Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/etiologia , Sistema Nervoso Autônomo/fisiopatologia , Atrofia de Múltiplos Sistemas/classificação , Atrofia de Múltiplos Sistemas/complicações , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Onset of genetically determined neurodegenerative diseases is difficult to specify because of their insidious and slowly progressive nature. This is especially true for spinocerebellar ataxia (SCA) because of varying affection of many parts of the nervous system and huge variability of symptoms. We investigated early symptoms in 287 patients with SCA1, SCA2, SCA3, or SCA6 and calculated the influence of CAG repeat length on age of onset depending on (1) the definition of disease onset, (2) people defining onset, and (3) duration of symptoms. Gait difficulty was the initial symptom in two-thirds of patients. Double vision, dysarthria, impaired hand writing, and episodic vertigo preceded ataxia in 4% of patients, respectively. Frequency of other early symptoms did not differ from controls and was regarded unspecific. Data about disease onset varied between patients and relatives for 1 year or more in 44% of cases. Influence of repeat length on age of onset was maximum when onset was defined as beginning of permanent gait disturbance and cases with symptoms for more than 10 years were excluded. Under these conditions, CAG repeat length determined 64% of onset variability in SCA1, 67% in SCA2, 46% in SCA3, and 41% in SCA6 demonstrating substantial influence of nonrepeat factors on disease onset in all SCA subtypes. Identification of these factors is of interest as potential targets for disease modifying compounds. In this respect, recognition of early symptoms that develop before onset of ataxia is mandatory to determine the shift from presymptomatic to affected status in SCA.
Assuntos
Ataxias Espinocerebelares , Expansão das Repetições de Trinucleotídeos/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ataxina-1 , Ataxina-3 , Ataxinas , Canais de Cálcio/genética , Análise Mutacional de DNA , Feminino , Transtornos Neurológicos da Marcha/complicações , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Ataxias Espinocerebelares/classificação , Ataxias Espinocerebelares/complicações , Ataxias Espinocerebelares/genética , Adulto JovemRESUMO
Spinocerebellar ataxias (SCAs) comprise a clinically and genetically heterogeneous group of autosomal dominantly inherited neurodegenerative disorders affecting the cerebellum and to variable degrees further parts of the nervous system. Electrophysiology is a potent tool to prove impairment of multiple neuronal systems and fibre tracts and even to decipher subclinical affection. Electrooculography, evoked potentials, nerve conduction studies and polysomnography are especially helpful in the setting of SCAs. Severely slowed saccades are a hallmark of SCA2. Vertical nystagmus occurs most frequently in SCA3 and SCA6. Visual potentials recede especially in SCA7. Substantially prolonged central motor conduction times in motor-evoked potentials occur frequently in SCA1 even in patients without clinical signs of pyramidal affection. Thus, electrophysiological analyses may help to predict the SCA genotype and direct molecular genetic diagnostics. Polysomnography is a helpful tool in the analysis of sleep disorders and frequently helps to decipher treatable causes like periodic leg movement in sleep and REM sleep behaviour disorder in SCAs. Nerve conduction studies reveal sensory neuropathy in all common SCA subtypes, but to variable degrees. Age rather than CAG repeat length appears to be the most important determinant for neuropathy and makes sensory nerve action potentials a potential progression marker in SCA.
Assuntos
Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/fisiopatologia , Eletroencefalografia , Eletroculografia , Eletrofisiologia/métodos , Potenciais Evocados Auditivos/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Potenciais Evocados Visuais/fisiologia , Genes Dominantes , Genótipo , Alemanha/epidemiologia , Humanos , Condução Nervosa/fisiologia , Ataxias Espinocerebelares/genéticaRESUMO
OBJECTIVE: To quantify spinal cord atrophy and its impact on clinical disability in spinocerebellar ataxia (SCA) type 3 and 6. METHODS: Atrophy of the upper spinal cord was assessed by high resolution T1-weighted MRI of patients with SCA3 (n = 14) and SCA6 (n = 10). Furthermore, two groups of age- and sex-matched healthy control subjects (n = 24,) corresponding to the two SCA groups, were studied. Images were post-processed by a semi-automated volumetry method combining a marker based segmentation and an automatic histogram method facilitating highly reliable quantification and morphometry of the upper cervical cord in vivo. RESULTS: We found a significant reduction of normalized mean crosssectional area of the spinal cord in SCA3 (p < 0.0005), whereas in SCA6 patients normalized mean crosssectional area was in the normal range (p = 0.379). No correlation was found between spinal cord atrophy and disease duration as well as CAG repeat length in both subtypes. In SCA6 a negative dependency between clinical disability, as expressed by the International Cooperative Ataxia Rating Scale as a well established ataxia score, and the mean cross-sectional area was found (p = 0.02). A similar correlation was observed in SCA3 but did not reach statistical significance. CONCLUSION: Our results quantify for the first time in vivo spinal cord atrophy as a non-cerebellar neurodegenerative process in SCA3. Our results suggest MR volumetry of the upper cervical cord as a marker of functional importance in SCA3 and SCA6.