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1.
Proc Natl Acad Sci U S A ; 118(7)2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33568534

RESUMO

Prolonged medically induced coma (pMIC) is carried out routinely in intensive care medicine. pMIC leads to cognitive impairment, yet the underlying neuromorphological correlates are still unknown, as no direct studies of MIC exceeding ∼6 h on neural circuits exist. Here, we establish pMIC (up to 24 h) in adolescent and mature mice, and combine longitudinal two-photon imaging of cortical synapses with repeated behavioral object recognition assessments. We find that pMIC affects object recognition, and that it is associated with enhanced synaptic turnover, generated by enhanced synapse formation during pMIC, while the postanesthetic period is dominated by synaptic loss. Our results demonstrate major side effects of prolonged anesthesia on neural circuit structure.


Assuntos
Anestesia Geral/efeitos adversos , Encéfalo/patologia , Coma/patologia , Animais , Encéfalo/fisiopatologia , Cognição , Coma/fisiopatologia , Feminino , Masculino , Camundongos , Plasticidade Neuronal , Sinapses/patologia
2.
BMC Ophthalmol ; 23(1): 104, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36927406

RESUMO

PURPOSE: To compare the root mean square (RMS) of anterior corneal higher-order aberrations (HOAs) in ametropic and emmetropic eyes. METHODS: This retrospective observational study was conducted at the Department of Ophthalmology, Tishreen University Hospital, Latakia, Syria. Study eyes were divided into four groups based on refractive error: mild-to-moderate myopia, hypermetropia, myopic astigmatism, and emmetropic eyes as controls. The following anterior corneal HOAs were evaluated using the Scheimpflug-Placido Sirius (CSO, Italy) tomographer over 6 mm pupil: Root mean square (RMS) total corneal HOAs, RMS trefoil, RMS coma and RMS spherical aberrations. RESULTS: RMS values of total HOAs, trefoil and coma showed statistically significant differences in all four groups (P < 0.05, all). HOAs were noted to be lowest in the control group (0.18 ± 0.09, 011 ± 0.08 and 0.09 ± 0.08 µm, respectively) and highest in the myopic astigmatism group (0.31 ± 0.16, 0.15 ± 0.12, 0.17 ± 0.14 µm, respectively). RMS spherical aberration was lowest in the astigmatism group (0.00 ± 0.16 µm) with a statistically significant difference from that in the control group (0.05 ± 0.07 µm, P = 0.049). CONCLUSION: The mean RMS values of total HOAs, trefoil and coma were highest in the astigmatism group and lowest in the control group. However, spherical aberration was minimal in the astigmatism group. A better understanding and targeted treatment of higher-order aberrations in ametropic human eyes, and in particular eyes with astigmatism, may enhance visual quality and performance in the treatment of refractive errors. Recognising atypical HOAs may also assist in the early detection of pathological conditions such as keratoconus.


Assuntos
Astigmatismo , Aberrações de Frente de Onda da Córnea , Erros de Refração , Humanos , Astigmatismo/diagnóstico , Coma/patologia , Acuidade Visual , Córnea/patologia , Erros de Refração/diagnóstico , Topografia da Córnea , Aberrações de Frente de Onda da Córnea/diagnóstico
3.
Sud Med Ekspert ; 65(4): 24-27, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35947405

RESUMO

The objective of the study was to investigate and characterize the clinical presentation, and establish macroscopic diagnostic signs of diffuse axonal injury (DAI) in the early (up to 3 days) post-injury period. In DAI, coma develops immediately after head injury and persists for 3 days post-injury until death. The coma is accompanied by dominant primary stem neurological symptoms, hemodynamic and respiratory disturbances and does not progress to a vegetative state. Lifetime computed tomography reveals cerebral hemorrhage in 40.5% of cases. We established the macroscopic signs of head injury in DAI. For the postmortem diagnosis of DAI, a detailed macroscopic appearance of pathognomonic cerebral hemorrhages is given, which are most frequently (67.5%) localized in the corpus callosum (CC), namely in the area from its genu to the middle of the trunk (97%). A rational, improved scheme of excision of CC trunk areas for the histological study is proposed.


Assuntos
Lesões Encefálicas , Traumatismos Craniocerebrais , Lesão Axonal Difusa , Lesões Encefálicas/diagnóstico , Coma/complicações , Coma/patologia , Corpo Caloso/patologia , Traumatismos Craniocerebrais/patologia , Lesão Axonal Difusa/diagnóstico por imagem , Lesão Axonal Difusa/etiologia , Humanos
4.
BMC Neurol ; 21(1): 259, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215217

RESUMO

BACKGROUND: The optic nerve sheath diameter (ONSD) and ONSD/eyeball transverse diameter (ETD) ratio have been proven to be correlated with intracranial pressure. This study aimed to evaluate the prognostic roles of ONSD and the ONSD/ETD ratio in comatose patients with supratentorial lesions and to determine the relationship of these two indices with the prognosis of such patients. METHODS: A total of 54 comatose patients with supratentorial lesions and 50 healthy controls were retrospectively included in this study. ONSD and ETD were measured by unenhanced computed tomography (CT). The differences in ONSD and the ONSD/ETD ratio between the two groups were compared. The prognosis of comatose patients was scored using the Glasgow Outcome Scale (GOS) at the 3-month follow-up, and these patients were classified into good (GOS score ≥ 3) and poor (GOS score < 3) prognosis groups. The differences in ONSD and the ONSD/ETD ratio were compared between comatose patients with good prognoses and those with poor prognoses. RESULTS: The ONSD and ONSD/ETD ratios in the comatose patients were 6.30 ± 0.60 mm and 0.27 ± 0.03, respectively, and both were significantly greater than those in the healthy controls (5.10 ± 0.47 mm, t = 11.426, P < 0.0001; 0.22 ± 0.02, t = 11.468, P < 0.0001; respectively). ONSD in patients with poor prognosis was significantly greater than that in patients with good prognosis (6.40 ± 0.56 vs. 6.03 ± 0.61 mm, t = 2.197, P = 0.032). The ONSD/ETD ratio in patients with poor prognosis was significantly greater than that in patients with good prognosis (0.28 ± 0.02 vs. 0.26 ± 0.03, t = 2.622, P = 0.011). The area under the receiver operating characteristic (ROC) curve, used to predict the prognosis of comatose patients, was 0.650 (95% confidence interval (CI): 0.486-0.815, P = 0.078) for ONSD and 0.711 (95% CI: 0.548-0.874, P = 0.014) for the ONSD/ETD ratio. CONCLUSIONS: The ONSD and ONSD/ETD ratios were elevated in comatose patients. The ONSD/ETD ratio might be more valuable than ONSD in predicting the prognoses of comatose patients with supratentorial lesions.


Assuntos
Coma , Nervo Óptico , Neoplasias Supratentoriais , Coma/diagnóstico , Coma/patologia , Escala de Resultado de Glasgow , Humanos , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Supratentoriais/diagnóstico , Neoplasias Supratentoriais/patologia
5.
Acta Med Okayama ; 75(5): 631-636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703046

RESUMO

Anorexia nervosa (AN) is occasionally complicated with hypoglycemic coma, which may cause sudden death by unknown mechanisms. We present the case of a 36-year-old woman with recurrent comas and a nineteen-year history of AN. She was found in a coma with remarkable hypoglycemia (28 mg/dL). Her BMI was 11.1 kg/m2. Endocrine workup revealed extremely low serum levels of glucagon, IGF-I and insulin. Asymptomatic hypoglycemia occurred with liver injury in the refeeding process. An aberrant glucose metabolism due to liver damage might have been involved in her susceptibility to hypoglycemia. This case suggests a possible mechanism of hypoglycemic coma in AN.


Assuntos
Anorexia Nervosa/complicações , Coma/etiologia , Hipoglicemia/complicações , Adulto , Coma/patologia , Feminino , Humanos , Recidiva
6.
Crit Care Med ; 48(7): 1018-1025, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32371609

RESUMO

OBJECTIVES: Lateral displacement and impaired cerebral autoregulation are associated with worse outcomes following acute brain injury, but their effect on long-term clinical outcomes remains unclear. We assessed the relationship between lateral displacement, disturbances to cerebral autoregulation, and clinical outcomes in acutely comatose patients. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Neurocritical care unit of the Johns Hopkins Hospital. PATIENTS: Acutely comatose patients (Glasgow Coma Score ≤ 8). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebral oximetry index, derived from near-infrared spectroscopy multimodal monitoring, was used to evaluate cerebral autoregulation. Associations between lateral brain displacement, global cerebral autoregulation, and interhemispheric cerebral autoregulation asymmetry were assessed using mixed random effects models with random intercept. Patients were grouped by functional outcome, determined by the modified Rankin Scale. Associations between outcome group, lateral displacement, and cerebral oximetry index were assessed using multivariate linear regression. Increasing lateral brain displacement was associated with worsening global cerebral autoregulation (p = 0.01 septum; p = 0.05 pineal) and cerebral autoregulation asymmetry (both p < 0.001). Maximum lateral displacement during the first 3 days of coma was significantly different between functional outcome groups at hospital discharge (p = 0.019 pineal; p = 0.008 septum), 3 months (p = 0.026; p = 0.007), 6 months (p = 0.018; p = 0.010), and 12 months (p = 0.022; p = 0.012). Global cerebral oximetry index was associated with functional outcomes at 3 months (p = 0.019) and 6 months (p = 0.013). CONCLUSIONS: During the first 3 days of acute coma, increasing lateral brain displacement is associated with worsening global cerebral autoregulation and cerebral autoregulation asymmetry, and poor long-term clinical outcomes in acutely comatose patients. The impact of acute interventions on outcome needs to be explored.


Assuntos
Encéfalo/patologia , Coma/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Coma/diagnóstico por imagem , Coma/metabolismo , Feminino , Escala de Coma de Glasgow , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Oximetria , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
7.
Crit Care Med ; 48(8): e639-e647, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32697504

RESUMO

OBJECTIVES: Recovery from coma might critically depend on the structural and functional integrity of frontoparietal networks. We aimed to measure this integrity in traumatic brain injury and anoxo-ischemic (cardiac arrest) coma patients by using an original multimodal MRI protocol. DESIGN: Prospective cohort study. SETTING: Three Intensive Critical Care Units affiliated to the University in Toulouse (France). PATIENTS: We longitudinally recruited 43 coma patients (Glasgow Coma Scale at the admission < 8; 29 cardiac arrest and 14 traumatic brain injury) and 34 age-matched healthy volunteers. Exclusion criteria were disorders of consciousness lasting more than 30 days and focal brain damage within the explored brain regions. Patient assessments were conducted at least 2 days (5 ± 2 d) after complete withdrawal of sedation. All patients were followed up (Coma Recovery Scale-Revised) 3 months after acute brain injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Functional and structural MRI data were recorded, and the analysis was targeted on the posteromedial cortex, the medial prefrontal cortex, and the cingulum. Univariate analyses and machine learning techniques were used to assess diagnostic and predictive values. Coma patients displayed significantly lower medial prefrontal cortex-posteromedial cortex functional connectivity (area under the curve, 0.94; 95% CI, 0.93-0.95). Cardiac arrest patients showed specific structural disturbances within posteromedial cortex. Significant cingulum architectural disturbances were observed in traumatic brain injury patients. The machine learning medial prefrontal cortex-posteromedial cortex multimodal classifier had a significant predictive value (area under the curve, 0.96; 95% CI, 0.95-0.97), best combination of subregions that discriminates a binary outcome based on Coma Recovery Scale-Revised). CONCLUSIONS: This exploratory study suggests that frontoparietal functional disconnections are specifically observed in coma and their structural counterpart provides information about brain injury mechanisms. Multimodal MRI biomarkers of frontoparietal disconnection predict 3-month outcome in our sample. These findings suggest that fronto-parietal disconnection might be particularly relevant for coma outcome prediction and could inspire innovative precision medicine approaches.


Assuntos
Coma Pós-Traumatismo da Cabeça/patologia , Coma/patologia , Lobo Frontal/patologia , Lobo Parietal/patologia , Adulto , Idoso , Estudos de Casos e Controles , Coma/diagnóstico por imagem , Coma/etiologia , Coma/fisiopatologia , Coma Pós-Traumatismo da Cabeça/diagnóstico por imagem , Coma Pós-Traumatismo da Cabeça/fisiopatologia , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Escala de Coma de Glasgow , Parada Cardíaca/complicações , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Estudos Prospectivos , Adulto Jovem
8.
Curr Opin Infect Dis ; 31(1): 69-77, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29206655

RESUMO

PURPOSE OF REVIEW: Cerebral impairment and acute kidney injury (AKI) are independent predictors of mortality in both adults and children with severe falciparum malaria. In this review, we present recent advances in understanding the pathophysiology, clinical features, and management of these complications of severe malaria, and discuss future areas of research. RECENT FINDINGS: Cerebral malaria and AKI are serious and well recognized complications of severe malaria. Common pathophysiological pathways include impaired microcirculation, due to sequestration of parasitized erythrocytes, systemic inflammatory responses, and endothelial activation. Recent MRI studies show significant brain swelling in both adults and children with evidence of posterior reversible encephalopathy syndrome-like syndrome although targeted interventions including mannitol and dexamethasone are not beneficial. Recent work shows association of cell-free hemoglobin oxidation stress involved in the pathophysiology of AKI in both adults and children. Paracetamol protected renal function likely by inhibiting cell-free-mediated oxidative stress. It is unclear if heme-mediated endothelial activation or oxidative stress is involved in cerebral malaria. SUMMARY: The direct causes of cerebral and kidney dysfunction remain incompletely understood. Optimal treatment involves prompt diagnosis and effective antimalarial treatment with artesunate. Renal replacement therapy reduces mortality in AKI but delayed diagnosis is an issue.


Assuntos
Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/terapia , Coma/fisiopatologia , Coma/terapia , Malária Falciparum/complicações , Acetaminofen/administração & dosagem , Injúria Renal Aguda/patologia , Animais , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Coma/patologia , Dexametasona/administração & dosagem , Modelos Animais de Doenças , Humanos , Rim/patologia , Manitol/administração & dosagem , Estresse Oxidativo , Resultado do Tratamento
9.
Crit Care Med ; 45(8): e763-e771, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28272153

RESUMO

OBJECTIVES: We hypothesize that the combined use of MRI cortical thickness measurement and subcortical gray matter volumetry could provide an early and accurate in vivo assessment of the structural impact of cardiac arrest and therefore could be used for long-term neuroprognostication in this setting. DESIGN: Prospective cohort study. SETTING: Five Intensive Critical Care Units affiliated to the University in Toulouse (France), Paris (France), Clermont-Ferrand (France), Liège (Belgium), and Monza (Italy). PATIENTS: High-resolution anatomical T1-weighted images were acquired in 126 anoxic coma patients ("learning" sample) 16 ± 8 days after cardiac arrest and 70 matched controls. An additional sample of 18 anoxic coma patients, recruited in Toulouse, was used to test predictive model generalization ("test" sample). All patients were followed up 1 year after cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cortical thickness was computed on the whole cortical ribbon, and deep gray matter volumetry was performed after automatic segmentation. Brain morphometric data were employed to create multivariate predictive models using learning machine techniques. Patients displayed significantly extensive cortical and subcortical brain volumes atrophy compared with controls. The accuracy of a predictive classifier, encompassing cortical and subcortical components, has a significant discriminative power (learning area under the curve = 0.87; test area under the curve = 0.96). The anatomical regions which volume changes were significantly related to patient's outcome were frontal cortex, posterior cingulate cortex, thalamus, putamen, pallidum, caudate, hippocampus, and brain stem. CONCLUSIONS: These findings are consistent with the hypothesis of pathologic disruption of a striatopallidal-thalamo-cortical mesocircuit induced by cardiac arrest and pave the way for the use of combined brain quantitative morphometry in this setting.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Parada Cardíaca/patologia , Adulto , Córtex Cerebelar/diagnóstico por imagem , Córtex Cerebelar/patologia , Coma/diagnóstico por imagem , Coma/patologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
10.
Curr Opin Crit Care ; 23(3): 244-250, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28323720

RESUMO

PURPOSE OF REVIEW: Delayed awakening after targeted temperature management (TTM) and sedation is frequent among cardiac arrest patients. Differentiating between prolonged coma and irreversible cerebral damage can be challenging, therefore the utilization of a multimodal approach is recommended by international guidelines. Here, we discuss indications and advantages/disadvantages of available modalities for coma prognostication and describe new tools to improve our accuracy for outcome prediction. RECENT FINDINGS: Studies from the TTM era confirmed that combining neurological examination with electrophysiological assessment [electroencephalography (EEG) and somato-sensory evoked potentials (SSEP)] greatly improves coma prognostication. This combination is nowadays recognized as the most useful by many clinicians and appears widely applicable as part of initial patient assessment. Additional tests (serum neuron specific enolase and neuroimaging) may be most useful to orient clinical decisions in patients with prolonged coma. Advanced analysis of EEG and SSEP recordings and the emergence of quantitative pupillometry hold great promise. SUMMARY: Multimodal prognostication offers a comprehensive approach of anoxic-ischemic encephalopathy and is increasingly used in postresuscitation care. Worldwide implementation and future advancements of available modalities, together with the increasing use of novel automated devices for quantitative neurological examination, may further optimize prognostic accuracy in the early ICU phase following cardiac arrest.


Assuntos
Coma/patologia , Coma/terapia , Parada Cardíaca/complicações , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/patologia , Hipóxia-Isquemia Encefálica/terapia , Temperatura , Coma/etiologia , Eletroencefalografia , Potenciais Somatossensoriais Evocados , Parada Cardíaca/terapia , Humanos , Hipóxia-Isquemia Encefálica/complicações , Prognóstico
11.
Ann Neurol ; 78(1): 68-76, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25893530

RESUMO

OBJECTIVE: What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brain pathology-thereby possibly providing a mechanistic framework for patient diagnosis, prognosis, and treatment development. METHODS: Structural T1-weighted magnetic resonance images were collected, in a continuous sample of 143 severely brain-injured patients with DOC (and 96 volunteers), across 2 tertiary expert centers. Brain atrophy in subcortical regions (bilateral thalamus, basal ganglia, hippocampus, basal forebrain, and brainstem) was assessed across (1) healthy volunteers and patients, (2) clinical entities (eg, vegetative state, minimally conscious state), (3) clinical measures of consciousness (Coma Recovery Scale-Revised), and (4) injury etiology. RESULTS: Compared to volunteers, patients exhibited significant atrophy across all structures (p < 0.05, corrected). Strikingly, we found almost no significant differences across clinical entities. Nonetheless, the clinical measures of awareness and wakefulness upon which differential diagnosis rely were systematically associated with tissue atrophy within thalamic and basal ganglia nuclei, respectively; the basal forebrain was atrophied in proportion to patients' response to sensory stimulation. In addition, nontraumatic injuries exhibited more extensive thalamic atrophy. INTERPRETATION: These findings provide, for the first time, a grounding in pathology for gold standard behavior-based clinical measures of consciousness, and reframe our current models of DOC by stressing the different links tying thalamic mechanisms to willful behavior and extrathalamic mechanisms to behavioral (and electrocortical) arousal.


Assuntos
Conscientização/fisiologia , Lesões Encefálicas/patologia , Encéfalo/patologia , Coma/patologia , Transtornos da Consciência/patologia , Estado de Consciência/fisiologia , Vigília/fisiologia , Adolescente , Adulto , Idoso , Atrofia , Prosencéfalo Basal/patologia , Prosencéfalo Basal/fisiopatologia , Gânglios da Base/patologia , Gânglios da Base/fisiopatologia , Encéfalo/fisiopatologia , Lesões Encefálicas/complicações , Lesões Encefálicas/fisiopatologia , Mapeamento Encefálico , Tronco Encefálico/patologia , Tronco Encefálico/fisiopatologia , Estudos de Casos e Controles , Coma/etiologia , Coma/fisiopatologia , Transtornos da Consciência/etiologia , Transtornos da Consciência/fisiopatologia , Estudos Transversais , Feminino , Hipocampo/patologia , Hipocampo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estado Vegetativo Persistente/etiologia , Estado Vegetativo Persistente/patologia , Estado Vegetativo Persistente/fisiopatologia , Índice de Gravidade de Doença , Tálamo/patologia , Tálamo/fisiopatologia , Adulto Jovem
12.
Brain ; 138(Pt 9): 2619-31, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26117367

RESUMO

Despite advances in resting state functional magnetic resonance imaging investigations, clinicians remain with the challenge of how to implement this paradigm on an individualized basis. Here, we assessed the clinical relevance of resting state functional magnetic resonance imaging acquisitions in patients with disorders of consciousness by means of a systems-level approach. Three clinical centres collected data from 73 patients in minimally conscious state, vegetative state/unresponsive wakefulness syndrome and coma. The main analysis was performed on the data set coming from one centre (Liège) including 51 patients (26 minimally conscious state, 19 vegetative state/unresponsive wakefulness syndrome, six coma; 15 females; mean age 49 ± 18 years, range 11-87; 16 traumatic, 32 non-traumatic of which 13 anoxic, three mixed; 35 patients assessed >1 month post-insult) for whom the clinical diagnosis with the Coma Recovery Scale-Revised was congruent with positron emission tomography scanning. Group-level functional connectivity was investigated for the default mode, frontoparietal, salience, auditory, sensorimotor and visual networks using a multiple-seed correlation approach. Between-group inferential statistics and machine learning were used to identify each network's capacity to discriminate between patients in minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Data collected from 22 patients scanned in two other centres (Salzburg: 10 minimally conscious state, five vegetative state/unresponsive wakefulness syndrome; New York: five minimally conscious state, one vegetative state/unresponsive wakefulness syndrome, one emerged from minimally conscious state) were used to validate the classification with the selected features. Coma Recovery Scale-Revised total scores correlated with key regions of each network reflecting their involvement in consciousness-related processes. All networks had a high discriminative capacity (>80%) for separating patients in a minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Among them, the auditory network was ranked the most highly. The regions of the auditory network which were more functionally connected in patients in minimally conscious state compared to vegetative state/unresponsive wakefulness syndrome encompassed bilateral auditory and visual cortices. Connectivity values in these three regions discriminated congruently 20 of 22 independently assessed patients. Our findings point to the significance of preserved abilities for multisensory integration and top-down processing in minimal consciousness seemingly supported by auditory-visual crossmodal connectivity, and promote the clinical utility of the resting paradigm for single-patient diagnostics.


Assuntos
Encéfalo/irrigação sanguínea , Transtornos da Consciência/patologia , Vias Neurais/irrigação sanguínea , Estado Vegetativo Persistente/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Criança , Coma/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Vias Neurais/patologia , Oxigênio/sangue , Descanso , Índice de Gravidade de Doença , Adulto Jovem
13.
Endocr J ; 63(6): 523-32, 2016 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-26924647

RESUMO

Myxedema coma (MC) is a life-threatening endocrine crisis caused by severe hypothyroidism. However, validated diagnostic criteria and treatment guidelines for MC have not been established owing to its rarity. Therefore, a valid animal model is required to investigate the pathologic and therapeutic aspects of MC. The aim of the present study was to establish an animal model of MC induced by total thyroidectomy. We utilized 14 male New Zealand White rabbits anesthetized via intramuscular ketamine and xylazine administration. A total of 7 rabbits were completely thyroidectomized under a surgical microscope (thyroidectomized group) and the remainder underwent sham operations (control group). The animals in both groups were monitored without thyroid hormone replacement for 15 weeks. Pulse rate, blood pressure, body temperature, and electrocardiograms (ECG) were recorded and blood samples were taken from the jugular vein immediately prior to the thyroidectomy and 2 and 4 weeks after surgery. The thyroidectomized rabbits showed a marked reduction of serum thyroxine levels at 4 weeks after the surgical procedure vs. controls (0.50±0.10 vs. 3.32±0.68 µg/dL, p<0.001). Additionally, thyroidectomized rabbits exhibited several signs of hypothyroidism such as hypothermia, systolic hypotension, bradycardia, and low voltage on ECGs, compared with controls. Of the 7 rabbits with severe hypothyroidism, 6 died from 4 to 14 weeks after the thyroidectomy possibly owing to heart failure, because histopathologic examinations revealed a myxedema heart. In summary, we have established a rabbit model of fatal hypothyroidism mimicking MC, which may facilitate pathophysiological and molecular investigations of MC and evaluations of new therapeutic interventions.


Assuntos
Coma/patologia , Modelos Animais de Doenças , Hipotireoidismo/patologia , Mixedema/patologia , Coelhos , Tireoidectomia/métodos , Animais , Coma/complicações , Diagnóstico Diferencial , Humanos , Masculino , Microdissecção , Mixedema/complicações , Índice de Gravidade de Doença , Tireoidectomia/veterinária
14.
Clin Infect Dis ; 60(1): 27-35, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25228706

RESUMO

BACKGROUND: Elevated endogenous plasma erythropoietin (EPO) levels have been associated with protection from acute neurologic deficits in Kenyan children with cerebral malaria (CM). Based on these findings and animal studies, clinical trials of recombinant human EPO (rHuEPO) have been started in children with CM. Recent clinical trials in adults with acute ischemic stroke have demonstrated increased mortality with rHuEPO treatment. We conducted a study in children with CM to assess the relationship of endogenous plasma and cerebrospinal fluid (CSF) EPO levels with mortality and acute and long-term neurologic outcomes. METHODS: A total of 210 children between 18 months and 12 years of age with a diagnosis of CM, were enrolled at Mulago Hospital, Kampala, Uganda. Plasma (n = 204) and CSF (n = 147) EPO levels at admission were measured by radioimmunoassay and compared with mortality and neurologic outcomes. RESULTS: After adjustment for age and hemoglobin level, a 1-natural-log increase in plasma EPO level was associated with a 1.74-fold increase in mortality (95% confidence interval, 1.09-2.77, P = .02). Plasma and CSF EPO levels also correlated positively with coma duration (P = .05 and P = .02, respectively). Plasma and CSF EPO levels did not differ in children with vs those without acute or long-term neurologic deficits. Plasma EPO levels correlated positively with markers of endothelial and platelet activation and histidine-rich protein-2 levels, but remained associated with mortality after adjustment for these factors. CONCLUSIONS: High endogenous plasma EPO levels are associated with prolonged coma duration and increased mortality in children >18 months of age with CM.


Assuntos
Coma/patologia , Eritropoetina/sangue , Malária Cerebral/complicações , Malária Cerebral/patologia , Líquido Cefalorraquidiano/química , Criança , Pré-Escolar , Eritropoetina/líquido cefalorraquidiano , Feminino , Humanos , Lactente , Masculino , Plasma/química , Prognóstico , Radioimunoensaio , Análise de Sobrevida , Uganda
15.
Proc Natl Acad Sci U S A ; 109(50): 20608-13, 2012 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-23185007

RESUMO

Human brain networks have topological properties in common with many other complex systems, prompting the following question: what aspects of brain network organization are critical for distinctive functional properties of the brain, such as consciousness? To address this question, we used graph theoretical methods to explore brain network topology in resting state functional MRI data acquired from 17 patients with severely impaired consciousness and 20 healthy volunteers. We found that many global network properties were conserved in comatose patients. Specifically, there was no significant abnormality of global efficiency, clustering, small-worldness, modularity, or degree distribution in the patient group. However, in every patient, we found evidence for a radical reorganization of high degree or highly efficient "hub" nodes. Cortical regions that were hubs of healthy brain networks had typically become nonhubs of comatose brain networks and vice versa. These results indicate that global topological properties of complex brain networks may be homeostatically conserved under extremely different clinical conditions and that consciousness likely depends on the anatomical location of hub nodes in human brain networks.


Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Coma/patologia , Coma/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas/complicações , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Estudos de Casos e Controles , Coma/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Adulto Jovem
16.
Brain Inj ; 29(13-14): 1729-35, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26517188

RESUMO

PRIMARY OBJECTIVE: To reveal covert abilities in a minimally conscious state (MCS) through an innovative activation paradigm based on olfactory imagery. RESEARCH DESIGN: Case study. METHODS AND PROCEDURES: A patient in MCS was asked to 'imagine an unpleasant odour' or to 'relax' in response to the appearance on a screen of a downward pointing arrow or a cross, respectively. Electrophysiological responses to stimuli were investigated by means of an 8-channel EEG equipment and analysed using a specific threshold algorithm. The protocol was repeated for 10 sessions separated from each other by 2 weeks. Accuracy, defined as the number of successes with respect to the total number of trials, was used to evaluate the number of times in which the classification strategy was successful. MAIN OUTCOMES AND RESULTS: Analyses of accuracy showed that the patient was able to activate and to relax himself purposefully and that he optimized his performances with the number of sessions, probably as a result of training-related improvements. CONCLUSIONS: Subtle signs of consciousness may be under-estimated and need to be revealed through specific activation tasks. This paradigm may be useful to detect covert signs of consciousness, especially when patients are precluded from carrying out more complex cognitive tasks.


Assuntos
Percepção Olfatória/fisiologia , Estado Vegetativo Persistente/fisiopatologia , Adulto , Encéfalo , Coma/patologia , Coma/fisiopatologia , Estado de Consciência/classificação , Estado de Consciência/fisiologia , Eletroencefalografia/métodos , Humanos , Masculino , Estado Vegetativo Persistente/diagnóstico , Prognóstico
17.
Genet Mol Res ; 14(2): 4914-9, 2015 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-25966266

RESUMO

This study aimed to observe the clinical curative effect of penehyclidine hydrochloride (PHC) combined with hemoperfusion in treating acute severe organophosphorus pesticide poisoning. We randomly divided 61 patients with severe organophosphorus pesticide poisoning into an experimental group (N = 31) and a control group (N = 30), and we compared the coma-recovery time, mechanical ventilation time, healing time, hospital expenses, and mortality between the two groups. The coma-recovery time, mechanical ventilation time, and healing time were lower in the experimental group than in the control group (P < 0.05), while the hospitalization expenses were higher in the experimental group than in the control group (P < 0.01); moreover, no significant difference was observed in the mortality rate between the two groups. Thus, PHC combined with hemoperfusion exerts a better therapeutic effect in acute severe organophosphorus pesticide poisoning than PHC alone.


Assuntos
Coma/tratamento farmacológico , Hemoperfusão , Intoxicação por Organofosfatos/tratamento farmacológico , Quinuclidinas/administração & dosagem , Adolescente , Adulto , Idoso , Coma/mortalidade , Coma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intoxicação por Organofosfatos/mortalidade , Intoxicação por Organofosfatos/patologia , Compostos Organofosforados/toxicidade , Praguicidas/intoxicação , Respiração Artificial
18.
Voen Med Zh ; 336(11): 37-47, 2015 Nov.
Artigo em Russo | MEDLINE | ID: mdl-30590900

RESUMO

The current conceptions of non- pharmacological therapeutic methods capabilities and mechanism of their action. The current article demonstrates the modern capabilities of non-pharmacological therapeutic methods on the example of effective use of infrared-terahertz radiation and acupuncture in cases when the standard treatments failed. The first clinical presentation describes the case of successful intervention in the stroke patient on his 18 day of staying in coma. The second presentation dedicates to rehabilitation of a post-stroke patient with hemiparesis and wheelchair use for five years. Then the modern approaches to understanding the employed methods are proposed. The developing concept is based on the idea that the applied therapeutic modalitiy forms an afferent matrix-challenge in the central nervous system to which the latter elaborates the reciprocal efferent matrix-response. In the process of reaction the central nervous system performs a kind of reboot of its system functional connections thus eliminating stagnant pathological dominants and inhibitions. It is proposed to employ the accumulated experience in the conditions of increasing restriction of drugs and medical devices import.


Assuntos
Aneurisma Aórtico/terapia , Modalidades de Fisioterapia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/terapia , Adulto , Idoso , Aneurisma Aórtico/patologia , Aneurisma Aórtico/fisiopatologia , Coma/patologia , Coma/fisiopatologia , Coma/terapia , Humanos , Masculino , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia
19.
Radiology ; 270(2): 506-16, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24471392

RESUMO

PURPOSE: To analyze white matter pathologic abnormalities by using diffusion-tensor (DT) imaging in a multicenter prospective cohort of comatose patients following cardiac arrest or traumatic brain injury (TBI). MATERIALS AND METHODS: Institutional review board approval and informed consent from proxies and control subjects were obtained. DT imaging was performed 5-57 days after insult in 49 cardiac arrest and 40 TBI patients. To control for DT imaging-processing variability, patients' values were normalized to those of 111 control subjects. Automated segmentation software calculated normalized axial diffusivity (λ1) and radial diffusivity (λ⊥) in 19 predefined white matter regions of interest (ROIs). DT imaging variables were compared by using general linear modeling, and side-to-side Pearson correlation coefficients were calculated. P values were corrected for multiple testing (Bonferroni). RESULTS: In central white matter, λ1 differed from that in control subjects in six of seven TBI ROIs and five of seven cardiac arrest ROIs (all P < .01). The λ⊥ differed from that in control subjects in all ROIs in both patient groups (P < .01). In hemispheres, λ1 was decreased compared with that in control subjects in three of 12 TBI ROIs (P < .05) and nine of 12 cardiac arrest ROIs (P < .01). The λ⊥ was increased in all TBI ROIs (P < .01) and in seven of 12 cardiac arrest ROIs (P < .05). Cerebral hemisphere λ1 was lower in cardiac arrest than in TBI in six of 12 ROIs (P < .01), while λ⊥ was higher in TBI than in cardiac arrest in eight of 12 ROIs (P < .01). Diffusivity values were symmetrically distributed in cardiac arrest (P < .001 for side-to-side correlation) but not in TBI patients. CONCLUSION: DT imaging findings are consistent with the known predominance of cerebral hemisphere axonal injury in cardiac arrest and chiefly central myelin injury in TBI. This consistency supports the validity of DT imaging for differentiating axon and myelin damage in vivo in humans.


Assuntos
Lesões Encefálicas/patologia , Imagem de Tensor de Difusão , Hipóxia-Isquemia Encefálica/patologia , Fibras Nervosas Mielinizadas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Coma/patologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
Curr Opin Crit Care ; 20(2): 168-73, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24531655

RESUMO

PURPOSE OF REVIEW: Data from MRI can be used to generate detailed maps of central nervous system anatomy and functional activation. Here, we review new research that integrates advanced MRI acquisition and analysis to predict and track recovery following severe traumatic brain injury (TBI) or anoxic ischemic encephalopathy (AIE) following cardiac arrest. RECENT FINDINGS: Diffusion tensor MRI studies of comatose TBI patients demonstrate specific distributions of white matter damage that are robustly associated with long-term functional outcomes. In unconscious patients with AIE, whole brain diffusion restriction has prognostic significance, as do regional changes in diffusion restriction or anisotropy. Results using functional MRI suggest that coma following TBI and cardiac arrest is associated with disconnections within cerebral architectures associated with arousal and conscious perception. The relation between these disconnections and postinjury recovery is being explored in ongoing cohorts. SUMMARY: MRI of the brain is feasible in critically ill patients following TBI or cardiac arrest, revealing patterns of structural damage and functional disconnection that can help predict outcome in the long term. Prospective studies are needed to validate these findings and to identify relationships between MRI-defined alterations and specific postinjury cognitive and behavioural phenotypes.


Assuntos
Lesões Encefálicas/patologia , Encéfalo/patologia , Coma/patologia , Imagem de Difusão por Ressonância Magnética , Hipóxia-Isquemia Encefálica/patologia , Imageamento por Ressonância Magnética , Encéfalo/fisiopatologia , Lesões Encefálicas/fisiopatologia , Feminino , Escala de Resultado de Glasgow , Parada Cardíaca/complicações , Parada Cardíaca/patologia , Parada Cardíaca/fisiopatologia , Humanos , Hipóxia-Isquemia Encefálica/fisiopatologia , Interpretação de Imagem Assistida por Computador , Masculino , Plasticidade Neuronal , Prognóstico , Recuperação de Função Fisiológica
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