RESUMO
OBJECTIVES: To investigate both cross-sectional and time-related changes of striatal and whole-brain microstructural properties in different stages of Huntington's disease (HD) using diffusion tensor imaging. EXPERIMENTAL DESIGN: From the TRACK-HD study, premanifest gene carriers (preHD), early manifest HD and controls were scanned at baseline and 2-year follow-up. Stratification of the preHD group into a far (preHD-A) and near (preHD-B) to predicted disease onset was performed. Age-corrected histograms of whole-brain white matter (WM), gray matter (GM) and striatal diffusion measures were computed and normalised by the number of voxels in each subject's data set. PRINCIPLE OBSERVATIONS: Higher cross-sectional mean, axial and radial diffusivities were found in both WM (P ≤ 0.001) and GM (P ≤ 0.001) of the manifest HD compared to the preHD and control groups. In preHD, only WM axial diffusivity (AD) was higher than in controls (P ≤ 0.01). This finding remained valid only in preHD-B (P ≤ 0.001). AD was also higher in the striatum of preHD-B compared to controls and preHD-A (P ≤ 0.01). Fractional anisotropy (FA) lacked sensitivity in differentiating between the groups. Histogram peak heights were generally lower in manifest HD compared to the preHD and control groups. No longitudinal differences were found in the degree of diffusivity change between the groups in the two year follow-up. There was a significant relationship between diffusivity and neurocognitive measures. CONCLUSIONS: Alterations in cross-sectional diffusion profiles between manifest HD subjects and controls were evident, both in whole-brain and striatum. In the preHD stage, only AD alterations were found, a finding suggesting that this metric is a sensitive marker for early change in HD prior to disease manifestation. The individual diffusivities were superior to FA in revealing pathologic microstructural brain alterations. Diffusion measures were well related to clinical functioning and disease stage.
Assuntos
Encéfalo/patologia , Doença de Huntington/patologia , Adulto , Anisotropia , Imagem de Tensor de Difusão , Feminino , Seguimentos , Substância Cinzenta/patologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Substância Branca/patologiaRESUMO
Patients suffering from narcolepsy type 1 show altered skin temperatures, resembling the profile that is related to sleep onset in healthy controls. The aim of the present study is to investigate the effects of sodium oxybate, a widely used drug to treat narcolepsy, on the 24-h profiles of temperature and sleep-wakefulness in patients with narcolepsy and controls. Eight hypocretin-deficient male narcolepsy type 1 patients and eight healthy matched controls underwent temperature measurement of core body and proximal and distal skin twice, and the sleep-wake state for 24 h. After the baseline assessment, 2 × 3 g of sodium oxybate was administered for 5 nights, immediately followed by the second assessment. At baseline, daytime core body temperature and proximal skin temperature were significantly lower in patients with narcolepsy (core: 36.8 ± 0.05 °C versus 37.0 ± 0.05 °C, F = 8.31, P = 0.01; proximal: 33.4 ± 0.26 °C versus 34.3 ± 0.26 °C, F = 5.66, P = 0.03). In patients, sodium oxybate administration increased proximal skin temperature during the day (F = 6.46, P = 0.04) to a level similar as in controls, but did not affect core body temperature, distal temperature or distal-proximal temperature gradient. Sodium oxybate administration normalised the predictive value of distal skin temperature and distal-proximal temperature gradient for the onset of daytime naps (P < 0.01). In conclusion, sodium oxybate administration resulted in a partial normalisation of the skin temperature profile, by increasing daytime proximal skin temperature, and by strengthening the known relationship between skin temperature and daytime sleep propensity. These changes seem to be related to the clinical improvement induced by sodium oxybate treatment. A causal relationship is not proven.
Assuntos
Regulação da Temperatura Corporal/efeitos dos fármacos , Narcolepsia/fisiopatologia , Temperatura Cutânea/efeitos dos fármacos , Oxibato de Sódio/farmacologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Narcolepsia/tratamento farmacológico , Orexinas/deficiência , Sono/efeitos dos fármacos , Sono/fisiologia , Oxibato de Sódio/administração & dosagem , Oxibato de Sódio/uso terapêutico , Fatores de Tempo , Vigília/efeitos dos fármacos , Vigília/fisiologia , Adulto JovemRESUMO
Narcolepsy with hypocretin deficiency is known to alter cardiovascular control during sleep, but its aetiology is disputed. As cardiovascular control differs between sleep states, and narcolepsy affects sleep architecture, controlling for both duration and transitions of sleep states is necessary. This study therefore aimed to assess heart rate and its variability in narcolepsy during sleep taking these factors into account. The study included 12 medication-naïve patients with narcolepsy with cataplexy and hypocretin deficiency (11 male, 16-53 years old), and 12 sex- and age-matched healthy controls (11 male, 19-55 years). All subjects underwent 1-night ambulatory polysomnography recording. Cardiovascular parameters were calculated for each 30-s epoch. Heart rate was significantly higher in patients with narcolepsy than in controls in all sleep states and during wakefulness prior to sleep. Groups did not differ in heart rate variability measures. The effects of sleep state duration on heart rate and its variability were similar between patients and controls. In conclusion, heart rate was consistently higher in patients with narcolepsy than controls, independent of sleep stage and sleep fragmentation. A direct effect of hypocretin deficiency therefore seems probable.
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Sistema Nervoso Autônomo/fisiopatologia , Cataplexia/complicações , Cataplexia/fisiopatologia , Frequência Cardíaca/fisiologia , Privação do Sono/complicações , Adolescente , Adulto , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Masculino , Pessoa de Meia-Idade , Neuropeptídeos/deficiência , Orexinas , Polissonografia , Respiração , Privação do Sono/fisiopatologia , Fases do Sono/fisiologia , Fatores de Tempo , Vigília/fisiologia , Adulto JovemRESUMO
The effects of hyperventilation (HV) on mean arterial pressure (MAP) are variable. To identify factors affecting the MAP response to HV, we dissected the effects of hypocapnic HV (HHV) and isocapnic HV (IHV) and evaluated the effects of acute vs. prolonged HHV. In 11 healthy subjects the cardio- and cerebrovascular effects of HHV and IHV vs. normal ventilation were examined for 15 min in the supine position and also for 15 min during 60 degrees head-up tilt. The end-tidal CO(2) of the HHV condition was set at 15-20 mmHg. With HHV in the supine position, mean cerebral blood flow velocity (mCBFV) declined [95% confidence interval (CI) -43 to -34%], heart rate (HR) increased (95% CI 7 to 16 beats/min), but MAP did not change (95% CI -1 to 6 mmHg). However, an augmentation of the supine MAP was observed in the last 10 min of HHV compared with the first 5 min of HHV (95% CI 2 to 12 mmHg). During HHV in the tilted position mCBFV declined (95% CI -28 to -12%) and MAP increased (95% CI 3 to 11 mmHg) without changes in HR. With supine IHV, mCBFV decreased (95% CI -14 to -4%) and MAP increased (95% CI 1 to 13 mmHg) without changes in HR. During IHV in the tilted position MAP was further augmented (95% CI 11 to 20 mmHg) without changes in CBFV or HR. Preventing hypocapnia during HV resulted in a higher MAP, suggesting two contrasting effects of HV on MAP: hypocapnia causing vasodepression and hyperpnea without hypocapnia acting as a vasopressor.
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Tontura/fisiopatologia , Hemodinâmica , Hiperventilação/fisiopatologia , Hipocapnia/fisiopatologia , Adolescente , Adulto , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Circulação Cerebrovascular , Feminino , Frequência Cardíaca , Humanos , Masculino , Postura , Ventilação Pulmonar , Decúbito Dorsal , Fatores de Tempo , Vasoconstrição , VasodilataçãoRESUMO
This exploratory follow-up study investigated whether EEG parameters can predict future cognitive performance. Forty elderly subjects, ranging from cognitively unimpaired to those with Alzheimer disease underwent EEG registration at baseline and neuropsychological examination at both baseline and follow-up. We assessed relations between EEG measures and future cognitive performance (i.e., global cognition, memory, language, and executive functioning) controlling for age, follow-up time, and baseline cognitive performance. Regression models were constructed to predict performance on the Cambridge Cognitive Examination, a widely used tool within dementia screenings. Baseline EEG measures, i.e., increased theta activity (4-8 Hz) during eyes closed and less alpha reactivity (8-13 Hz) during eyes open and memory activation, indicated lower global cognitive, language (trend significant), and executive performance at follow-up. A regression model combining baseline cognitive and EEG measures provided the best prediction of future Cambridge Cognitive Examination performance (93%). EEG and cognitive measures alone predicted, respectively, 43% and 92% of variance. EEG and cognitive measures combined provided the best prediction of future cognitive performance. Although the "cognition only" model showed similar predictive power, the EEG provided significant additional value. The added value of EEG registration in the diagnostic work-up of dementia should be further assessed in larger samples.
Assuntos
Envelhecimento/fisiologia , Transtornos Cognitivos/fisiopatologia , Cognição/fisiologia , Eletroencefalografia/métodos , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Transtornos Cognitivos/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valor Preditivo dos Testes , Análise de Regressão , Estudos RetrospectivosRESUMO
In this study we longitudinally investigated the rate of microstructural alterations in the occipital cortex in different stages of Huntington's disease (HD) by applying an automated atlas-based approach to diffusion MRI data. Twenty-two premanifest (preHD), 10 early manifest HD (early HD) and 24 healthy control subjects completed baseline and two year follow-up scans. The preHD group was stratified based on the predicted years to disease onset into a far (preHD-A) and near (preHD-B) to disease onset group. Clinical and behavioral measures were collected per assessment time point. An automated atlas-based DTI analysis approach was used to obtain the mean, axial and radial diffusivities of the occipital cortex. We found that the longitudinal rate of diffusivity change in the superior occipital gyrus (SOG), middle occipital gyrus (MOG), and inferior occipital gyrus (IOG) was significantly higher in early HD compared to both preHD and controls (all p's ≤ 0.005), which can be interpreted as an increased rate of microstructural degeneration. Furthermore, the change rate in the diffusivity of the MOG could significantly discriminate between preHD-B compared to preHD-A and the other groups (all p's ≤ 0.04). Finally, we found an inverse correlation between the Stroop Word Reading task and diffusivities in the SOG and MOG (all p's ≤ 0.01). These findings suggest that measures obtained from the occipital cortex can serve as sensitive longitudinal biomarkers for disease progression in preHD-B and early HD. These could in turn be used to assess potential effects of proposed disease modifying therapies.
Assuntos
Doença de Huntington/diagnóstico por imagem , Lobo Occipital/diagnóstico por imagem , Adulto , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Feminino , Seguimentos , Humanos , Doença de Huntington/fisiopatologia , Doença de Huntington/psicologia , Processamento de Imagem Assistida por Computador , Idioma , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Degeneração Neural , Lobo Occipital/fisiopatologia , Reconhecimento Automatizado de Padrão , Teste de StroopRESUMO
BACKGROUND: In Huntington's Disease (HD) cognitive decline can occur before unequivocal motor signs become apparent. As cognitive decline often starts early in the course of the disease and has a progressive nature over time, cognition can be regarded as a key target for symptomatic treatment. The specific progressive profile of cognitive decline over time is unknown. OBJECTIVE: The aim of this study is to quantify the progression of cognitive decline across all HD stages, from pre-motormanifest to advanced HD, and to investigate if CAG length mediates cognitive decline. METHODS: In the European REGISTRY study 2669 HD expansion gene carriers underwent annual cognitive assessment. General linear mixed models were used to model the cognitive decline for each cognitive task across all disease stages. Additionally, a model was developed to evaluate the cognitive decline based on CAG length and age rather than disease stage. RESULTS: There was significant cognitive decline on all administered tasks throughout pre-motormanifest (close to estimated disease onset) participants and the subsequent motormanifest participants from stage 1 to stage 4. Performance on the Stroop Word and Stroop Color tests additionally declined significantly across the two pre-motormanifest groups: far and close to estimated disease onset. The evaluation of cognition performance in relation to CAG length and age revealed a more rapid cognitive decline in participants with longer CAG length than participants with shorter CAG length over time. CONCLUSION: Cognitive performance already shows decline in pre-motormanifest HD gene expansion carriers and gradually worsens to late stage HD. HD gene expansion carriers with certain CAG length have their own cognitive profile, i.e., longer CAG length is associated with more rapid decline.
Assuntos
Cognição , Disfunção Cognitiva/genética , Heterozigoto , Doença de Huntington/genética , Expansão das Repetições de Trinucleotídeos , Adulto , Idoso , Disfunção Cognitiva/complicações , Progressão da Doença , Feminino , Humanos , Doença de Huntington/complicações , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
STUDY OBJECTIVES: Previous laboratory studies in narcolepsy patients showed altered core body and skin temperatures, which are hypothesised to be related to a disturbed sleep wake regulation. In this ambulatory study we assessed temperature profiles in normal daily life, and whether sleep attacks are heralded by changes in skin temperature. Furthermore, the effects of three months of treatment with sodium oxybate (SXB) were investigated. METHODS: Twenty-five narcolepsy patients and 15 healthy controls were included. Core body, proximal and distal skin temperatures, and sleep-wake state were measured simultaneously for 24 hours in ambulatory patients. This procedure was repeated in 16 narcolepsy patients after at least 3 months of stable treatment with SXB. RESULTS: Increases in distal skin temperature and distal-to-proximal temperature gradient (DPG) strongly predicted daytime sleep attacks (P < 0.001). As compared to controls, patients had a higher proximal and distal skin temperature in the morning, and a lower distal skin temperature during the night (all P < 0.05). Furthermore, they had a higher core body temperature during the first part of the night (P < 0.05), which SXB decreased (F = 4.99, df = 1, P = 0.03) to a level similar to controls. SXB did not affect skin temperature. CONCLUSIONS: This ambulatory study demonstrates that daytime sleep attacks were preceded by clear changes in distal skin temperature and DPG. Furthermore, changes in core body and skin temperature in narcolepsy, previously only studied in laboratory settings, were partially confirmed. Treatment with SXB resulted in a normalisation of the core body temperature profile. Future studies should explore whether predictive temperature changes can be used to signal or even prevent sleep attacks.
Assuntos
Temperatura Corporal/efeitos dos fármacos , Fármacos do Sistema Nervoso Central/uso terapêutico , Narcolepsia/tratamento farmacológico , Narcolepsia/fisiopatologia , Oxibato de Sódio/uso terapêutico , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Fármacos do Sistema Nervoso Central/farmacologia , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Narcolepsia/diagnóstico , Temperatura Cutânea/efeitos dos fármacos , Oxibato de Sódio/farmacologia , Resultado do Tratamento , Adulto JovemRESUMO
STUDY OBJECTIVES: The carotid bodies are thought to play an important role in sleep-dependent autonomic changes. Patients who underwent resection of bilateral carotid body tumors have chronically attenuated baroreflex sensitivity. These subjects provide a unique opportunity to investigate the role of the baroreflex during sleep. DESIGN: One-night ambulatory polysomnography (PSG) recording. SETTING: Participants' homes. PARTICIPANTS: Nine patients with bilateral carotid body tumor resection (bCBR) (four women, mean age 50.4 ± 7.2 years) and nine controls matched for age, gender, and body mass index. INTERVENTIONS: N/A. MEASUREMENTS: Sleep parameters were obtained from PSG. Heart rate (HR) and its variability were calculated using 30-s epochs. RESULTS: In bCBR patients, HR was slightly but not significantly increased during wake and all sleep stages. The effect of sleep on HR was similar for patients and controls. Low frequency (LF) power of the heart rate variability spectrum was significantly lower in bCBR patients in active wakefulness, sleep stage 1 and REM sleep. No differences were found between patients and controls for high frequency (HF) power and the LF/HF ratio. CONCLUSIONS: Bilateral carotid body tumor resection (bCBR) is associated with decreased low frequency power during sleep, suggesting impaired baroreflex function. Despite this, sleep-related heart rate changes were similar between bCBR patients and controls. These findings suggest that the effects of sleep on heart rate are predominantly generated through central, non-baroreflex mediated pathways.
Assuntos
Barorreflexo/fisiologia , Tumor do Corpo Carotídeo/cirurgia , Corpo Carotídeo/cirurgia , Frequência Cardíaca/fisiologia , Sono/fisiologia , Sistema Nervoso Autônomo/fisiologia , Índice de Massa Corporal , Corpo Carotídeo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Fases do Sono/fisiologia , Vigília/fisiologiaRESUMO
Many efforts have been directed at negating the influence of electromyographic (EMG) activity on the EEG, especially in elderly demented patients. We wondered whether these "artifacts" might reflect cognitive and behavioural aspects of dementia. In this pilot study, 11 patients with probable Alzheimer's disease (AD), 13 with amnestic mild cognitive impairment (MCI) and 13 controls underwent EEG registration. As EMG measures, we used frontal and temporal 50-70 Hz activity. We found that the EEGs of AD patients displayed more theta activity, less alpha reactivity, and more frontal EMG than controls. Interestingly, increased EMG activity indicated more cognitive impairment and more depressive complaints. EEG variables on the whole distinguished better between groups than EMG variables, but an EMG variable was best for the distinction between MCI and controls. Our results suggest that EMG activity in the EEG could be more than noise; it differs systematically between groups and may reflect different cerebral functions than the EEG.
RESUMO
The EEG is potentially useful as a marker of early Huntington's disease (HD). In dementia, the EEG during a memory activation challenge showed abnormalities where the resting EEG did not. We investigated whether memory activation also reveals EEG abnormalities in preclinical HD. Sixteen mutation carriers for HD and 13 nonmutation carriers underwent neurological, neuropsychological, MRI and EEG investigations. The EEG was registered during a rest condition, i.e. eyes closed, and a working memory task. In each condition we determined absolute power in the theta (4-8 Hz) and alpha (8-13 Hz) bands and subsequently calculated relative alpha power. The EEG during eyes closed did not differ between groups. The EEG during memory activation showed less relative alpha power in mutation carriers as compared to nonmutation carriers, even though memory performance was similar [F (1,27) = 10.87; P = 0.003]. Absolute powers also showed less alpha power [F (1,27) = 7.02; P = 0.013] but similar theta power. No correlations were found between absolute and relative alpha power on the one hand and neuropsychological scores, motor scores or number of CAG repeats on the other. In conclusion, memory activation reveals functional brain changes in Huntington's disease before clinical signs become overt.
Assuntos
Córtex Cerebral/fisiopatologia , Eletroencefalografia , Doença de Huntington/diagnóstico , Memória de Curto Prazo/fisiologia , Adulto , Ritmo alfa , Diagnóstico Precoce , Feminino , Triagem de Portadores Genéticos , Humanos , Doença de Huntington/genética , Doença de Huntington/fisiopatologia , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Testes Neuropsicológicos , Valor Preditivo dos Testes , Ritmo Teta , Repetições de TrinucleotídeosRESUMO
We report a 20-year-old sportsman with frequent attacks of lightheadedness, chest pain, blurred vision and falls during and shortly after exercise. Cardiac and pulmonal evaluation and routine autonomic function tests were normal apart from a relatively high resting heart rate (70 bpm) compared to endurance-trained men. In view of the relation to exercise, the patient was asked to cycle with maximal effort on an ergometer with continuous blood pressure (BP), heart rate (HR) and electroencephalogram (EEG) registration. Immediately after cessation of exercise a brief hypotensive period (75/45 mmHg) occurred together with sinus tachycardia (180 bpm) during which the patient experienced his typical complaints. We hypothesized that our patient's symptoms were primary related to sympathetic failure. As water drinking has been demonstrated to raise sympathetic activity rapidly, we undertook a second cycling test after ingestion of 1000 mL tap water. Symptoms nor hypotension recurred. Because of the short lasting pressor effect and its minimal side effects, we suggest water drinking as simple and possible effective therapy for idiopathic exercise-related syncope.