Cerebral Hypoperfusion in Posterior Reversible Encephalopathy Syndrome is Different from Transient Ischemic Attack on CT Perfusion.

BACKGROUND: PRES is a reversible neurotoxic state presenting with headache, altered mental status, visual loss, and seizures. Delayed diagnosis can be avoided if radiological patterns could distinguish PRES from cerebral ischemia. METHODS: Clinical and radiological data were collected on all hospitalized patients who had (1) discharge diagnosis of PRES and (2) acute CTP/CTA. Data were compared with 10 TIA patients with proven cytotoxic edema on MRI. RESULTS: Of the four PRES patients found, three were correlated with acute blood pressure and one with chemotherapy. At the radiological level, quantitative analyses of the CTP parameters showed that 2 out of 4 patients had bilaterally reduced CBF-values (23.2-47.1 ml/100g/min) in occipital regions, as seen in the pathological regions of TIA patients (27.3 ± 13.5 ml/100g/min). When compared with TIA patients, the pathological ROI's demonstrated decreased CBV-values (3.4-5.6 ml/100g). Vasogenic edema on MRI FLAIR imaging was seen in only one PRES patient, and cytotoxic edema on DWI-imaging was never found. CT angiography showed in one PRES patient a vasospasm-like unilateral posterior cerebral artery. CONCLUSIONS: If confirmed by other groups, CTP and CTA imaging in patients with acute visual loss and confusion may help to distinguish PRES from bi-occipital ischemia. These radiological parameters may identify PRES patients at risk for additional tissue infarction.

Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling.

Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction. To investigate possible underlying mechanisms we analyzed the molecular alterations in histopathological normal appearing cortical gray matter (NAGM) in MS. By performing a differential gene expression analysis of NAGM of control and MS cases we identified reduced transcription of astrocyte specific genes involved in the astrocyte-neuron lactate shuttle (ANLS) and the glutamate-glutamine cycle (GGC). Additional quantitative immunohistochemical analysis demonstrating a CX43 loss in MS NAGM confirmed a crucial involvement of astrocytes and emphasizes their importance in MS pathogenesis. Concurrently, a Toll-like/IL-1β signaling expression signature was detected in MS NAGM, indicating that immune-related signaling might be responsible for the downregulation of ANLS and GGC gene expression in MS NAGM. Indeed, challenging astrocytes with immune stimuli such as IL-1β and LPS reduced their ANLS and GGC gene expression in vitro. The detected upregulation of IL1B in MS NAGM suggests inflammasome priming. For this reason, astrocyte cultures were treated with ATP and ATP/LPS as for inflammasome activation. This treatment led to a reduction of ANLS and GGC gene expression in a comparable manner. To investigate potential sources for ANLS and GGC downregulation in MS NAGM, we first performed an adjuvant-driven stimulation of the peripheral immune system in C57Bl/6 mice in vivo. This led to similar gene expression changes in spinal cord demonstrating that peripheral immune signals might be one source for astrocytic gene expression changes in the brain. IL1B upregulation in MS NAGM itself points to a possible endogenous signaling process leading to ANLS and GGC downregulation. This is supported by our findings that, among others, MS NAGM astrocytes express inflammasome components and that astrocytes are capable to release Il-1β in-vitro. Altogether, our data suggests that immune signaling of immune- and/or central nervous system origin drives alterations in astrocytic ANLS and GGC gene regulation in the MS NAGM. Such a mechanism might underlie cortical brain dysfunctions frequently encountered in MS patients.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: effect of Anticoagulation and Its Timing: the RAF Study.

BACKGROUND AND PURPOSE: The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. METHODS: The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. RESULTS: Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). CONCLUSIONS: Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.

Synaptic depression and slow oscillatory activity in a biophysical network model of the cerebral cortex

Short-term synaptic depression (STD) is a form of synaptic plasticity that has a large impact on network computations. Experimental results suggest that STD is modulated by cortical activity, decreasing with activity in the network and increasing during silent states. Here, we explored different activity-modulation protocols in a biophysical network model for which the model displayed less STD when the network was active than when it was silent, in agreement with experimental results. Furthermore, we studied how trains of synaptic potentials had lesser decay during periods of activity (UP states) than during silent periods (DOWN states), providing new experimental predictions. We next tackled the inverse question of what is the impact of modifying STD parameters on the emergent activity of the network, a question difficult to answer experimentally. We found that synaptic depression of cortical connections had a critical role to determine the regime of rhythmic cortical activity. While low STD resulted in an emergent rhythmic activity with short UP states and long DOWN states, increasing STD resulted in longer and more frequent UP states interleaved with short silent periods. A still higher synaptic depression set the network into a non-oscillatory firing regime where DOWN states no longer occurred. The speed of propagation of UP states along the network was not found to be modulated by STD during the oscillatory regime; it remained relatively stable over a range of values of STD. Overall, we found that the mutual interactions between synaptic depression and ongoing network activity are critical to determine the mechanisms that modulate cortical emergent patterns.

Neuronal death after perinatal cerebral hypoxia-ischemia: Focus on autophagy-mediated cell death.

Neonatal hypoxic-ischemic encephalopathy is a critical cerebral event occurring around birth with high mortality and neurological morbidity associated with long-term invalidating sequelae. In view of the great clinical importance of this condition and the lack of very efficacious neuroprotective strategies, it is urgent to better understand the different cell death mechanisms involved with the ultimate aim of developing new therapeutic approaches. The morphological features of three different cell death types can be observed in models of perinatal cerebral hypoxia-ischemia: necrotic, apoptotic and autophagic cell death. They may be combined in the same dying neuron. In the present review, we discuss the different cell death mechanisms involved in neonatal cerebral hypoxia-ischemia with a special focus on how autophagy may be involved in neuronal death, based: (1) on experimental models of perinatal hypoxia-ischemia and stroke, and (2) on the brains of human neonates who suffered from neonatal hypoxia-ischemia.

Gliossarcoma de tronco cerebral em paciente pediátrico: relato de caso

Os autores relatam o caso de um paciente branco, de quatro anos de idade, com comprometimento neurológico progressivo. Tomografia computadorizada do crânio e ressonância magnética evidenciaram lesão expansiva no tronco cerebral. Subseqüentemente, foi feito diagnóstico histopatológico de gliossarcoma. Trata-se de um tumor raro do sistema nervoso central que, na grande maioria dos casos, acomete pacientes acima dos 40 anos de idade e tem localização supratentorial. Há poucos casos relatados de gliossarcomas em crianças, sobretudo na região infratentorial. Dados epidemiológicos, assim como achados mais freqüentes na tomografia computadorizada e ressonância magnética, são discutidos.

Neuroenergetic Response to Prolonged Cerebral Glucose Depletion after Severe Brain Injury and the Role of Lactate.

Lactate may represent a supplemental fuel for the brain. We examined cerebral lactate metabolism during prolonged brain glucose depletion (GD) in acute brain injury (ABI) patients monitored with cerebral microdialysis (CMD). Sixty episodes of GD (defined as spontaneous decreases of CMD glucose from normal to low [<1.0 mmol/L] for at least 2 h) were identified among 26 patients. During GD, we found a significant increase of CMD lactate (from 4±2.3 to 5.4±2.9 mmol/L), pyruvate (126.9±65.1 to 172.3±74.1 μmol/L), and lactate/pyruvate ratio (LPR; 27±6 to 35±9; all, p<0.005), while brain oxygen and blood lactate remained normal. Dynamics of lactate and glucose supply during GD were further studied by analyzing the relationships between blood and CMD samples. There was a strong correlation between blood and brain lactate when LPR was normal (r=0.56; p<0.0001), while an inverse correlation (r=-0.11; p=0.04) was observed at elevated LPR >25. The correlation between blood and brain glucose also decreased from r=0.62 to r=0.45. These findings in ABI patients suggest increased cerebral lactate delivery in the absence of brain hypoxia when glucose availability is limited and support the concept that lactate acts as alternative fuel.

Hematoma intraparenquimatoso cerebral espontâneo: aspectos à tomografia computadorizada

OBJETIVO: Identificar os aspectos mais freqüentes do hematoma intraparenquimatoso cerebral espontâneo observados na tomografia computadorizada. MATERIAIS E MÉTODOS: Foram analisados, retrospectivamente, os exames de tomografia computadorizada de 250 pacientes com hematoma intraparenquimatoso cerebral espontâneo, provenientes de três diferentes hospitais da cidade do Rio de Janeiro. RESULTADOS: O hematoma intraparenquimatoso cerebral profundo foi o de maior incidência, equivalendo a 54,4% (136 casos), seguido do lobar com 34,8% (87 casos). Mais raramente, observou-se sangramento cerebelar em 8,4% (21 casos) e do tronco cerebral em 2,4% (seis casos) dos pacientes. CONCLUSÃO: A cefaléia foi o sintoma mais comum e a hipertensão arterial foi o sinal mais freqüentemente apresentado. A drenagem do hematoma para o sistema ventricular ocorreu mais comumente nos hematoma profundos.