Persisting vasculitis after pneumococcal meningitis

Introduction: Bacterial meningitis is associated with a high mortality and a high incidence of neurological sequelae. Parainfectious vasculitis leading to ischemic brain damage is a known complication of bacterial meningitis but its treatment is uncertain. Methods and Results: We report the case of a 53-year-old man with pneumococcal meningitis who developed numerous ischemic lesions in the brainstem and basal ganglia caused by parainfectious vasculitis. Clinical and radiological improvement was observed after delayed corticosteroid initiation. Symptomatic vasculitis relapsed after steroid withdrawal and stabilized after reintroduction of the immunosuppressive therapy. Although the cerebrospinal fluid (CSF) contained high levels of MMP-9 at the time of symptomatic vasculitis, a significant decrease of the enzyme accompanied the introduction of corticotherapy and the regression of vasculitic symptoms. No relation between the level of MMP-9 and the white blood cell count in CSF could be found. Conclusion: Parainfectious vasculitis may respond to late corticosteroid treatment. MMP-9 level in CSF may be a marker of vasculitic complication in bacterial meningiti

Plasma Concentrations of Brain-derived Neurotrophic Factor in Patients Undergoing Minor Surgery: A Randomized Controlled Trial

We measured perioperative plasma concentrations of brain-derived neurotrophic factor (BDNF), a major mediator of synaptic plasticity in the central nervous system, in males, 30-65 years old, undergoing lumbar or cervical discotomy. Patients were randomly allocated to a general anesthetic with propofol induction and maintenance or with thiopental induction and isoflurane maintenance. BDNF plasma concentrations were measured before induction (baseline), 15min after induction but before start of surgery, at skin closure, in the post-anesthetic care unit, and 24h postoperatively. Data from 26 patients (13 in each group) were analyzed. At each time point, BDNF plasma concentrations showed large variability. At baseline, concentrations were 631±337 (mean±SD)pgml−1 in the propofol group and were 549±512pgml−1 in the thiopental-isoflurane group (P=0.31). At 15min, concentrations significantly decreased in the propofol group (247±219pgml−1, P=0.0012 compared with baseline) but remained unchanged in the thiopental-isoflurane group (597±471pgml−1, P=0.798 compared with baseline). At skin closure and in the post-anesthetic care unit, concentrations were not different from baseline in both groups. At 24h, concentrations significantly decreased below baseline in both groups (propofol: 232±129pgml−1, P=0.0015; thiopental-isoflurane: 253±250pgml−1, P=0.016). In the propofol group, there was a weak but statistically significant positive correlation (R 2=0.38, P=0.026) between the duration of surgery and BDNF plasma concentrations at skin closure. These data suggest that in males undergoing elective minor surgery, BDNF plasma concentrations show a specific pattern that is influenced by the anesthetic technique and, possibly, by the duration of surger

Matrix metalloproteinase 9 and cellular fibronectin plasma concentrations are predictors of the composite endpoint of length of stay and death in the intensive care unit after severe traumatic brain injury

BACKGROUND: The relationship between severe traumatic brain injury (TBI) and blood levels of matrix metalloproteinase-9 (MMP-9) or cellular fibronectin (c-Fn) has never been reported. In this study, we aimed to assess whether plasma concentrations of MMP-9 and c-Fn could have predictive values for the composite endpoint of intensive care unit (ICU) length of stay (LOS) of survivors and mortality after severe TBI. Secondary outcomes were the state of consciousness measured with the Glasgow Coma Scale (GCS) of survivors at 14 days and Glasgow Outcome Scale Extended (GOSE) at 3 months. METHODS: Forty-nine patients with abbreviated injury scores of the head region ≥ 4 were included. Blood was sampled at 6, 12, 24 and 48 hours after injury. MMP-9 and c-Fn concentrations were measured by ELISA. The values of MMP-9 and c-Fn, and, for comparison, the value of the GCS on the field of the accident (fGCS), as predictors of the composite outcome of ICU LOS and death were assessed by logistic regression. RESULTS: There was a linear relationship between maximal MMP-9 concentration, measured during the 6-12-hour period, and maximal c-Fn concentration, measured during the 24-48-hour period. The risk of staying longer than 9 days in the ICU or of dying was increased in patients with a maximal early MMP-9 concentration ≥ 21.6 ng/ml (OR = 5.0; 95% CI: 1.3 to 18.6; p = 0.02) or with a maximal late c-Fn concentration ≥ 7.7 μg/ml (OR = 5.4; 95% CI: 1.4 to 20.8; p = 0.01). A similar risk association was observed with fGCS ≤8 (OR, 4.4; 95% CI, 1.2-15.8; p = 0.02). No relationship was observed between MMP-9, c-Fn concentrations or fGCS and the GCS at 14 days of survivors and GOSE at 3 months. CONCLUSIONS: Plasma MMP-9 and c-Fn concentrations in the first 48 hours after injury are predictive for the composite endpoint of ICU LOS and death after severe TBI but not for consciousness at 14 days and outcome at 3 months

Effect of the duration of middle cerebral artery occlusion on the risk of hemorrhagic transformation after tissue plasminogen activator injection in rats

Thrombolysis with tissue plasminogen activator increases the risk of brain hemorrhage after ischemic stoke. However, the relationship between the duration of ischemia and the risk of hemorrhagic transformation is still unclear. In the present study, we used a rat model of thrombolysis with tissue plasminogen activator after different periods of middle cerebral artery occlusion and we analyzed the effect of the duration of ischemia on the rate of hemorrhagic transformation, the extent of cerebral infarction and the degree of neurological impairment. Most of the rats reperfused before 3 h of ischemia did not develop intracerebral hemorrhages, while 90% of the rats occluded for more than 3 h developed cerebral hemorrhages ranging from benign hemorrhagic infarctions to severe parenchymal hemorrhages. After 6-hour occlusion, the proportion of parenchymal hemorrhages, as seen in 50% of the animals, was significantly augmented compared to the 11 to 13% of parenchymal hemorrhages observed in animals occluded for less than 6 h. Meanwhile, the quantity of hemoglobin measured in the brain parenchyma of animals showing hemorrhagic infarctions was doubled (0.19 mg/hemisphere in rats reperfused after 6 h of ischemia compared to 0.08 mg/hemisphere in rats reperfused earlier). Neurological outcome did also worsen with the duration of ischemia. However, the amplitude of cerebral infarction was not statistically different in animals subjected to short or longer time of ischemia. In addition, the risk of hemorrhagic transformation and the degree of neurological impairment were not statistically different between animals occluded for less than 3 h and animals permanently occluded. Our data clearly demonstrate a progression in the risk and gravity of hemorrhagic transformation that parallels the increase in the duration of transient cerebral ischemia. The results suggest a relationship, which is independent on the duration of ischemia, between neurological deficit and hemorrhagic transformation and confirm the expected but still debated principle that early recanalization of an occluded artery reduces the hemorrhagic risk after thrombolysis with tissue plasminogen activator

Pronounced α-synuclein pathology in a seeding-based mouse model is not sufficient to induce mitochondrial respiration deficits in the striatum and amygdala

Increasing evidence suggests that crosstalk between α-synuclein pathology formation and mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson’s disease and related synucleinopathies. While mitochondrial dysfunction is a well-studied phenomenon in the substantia nigra, which is selectively vulnerable in Parkinson’s disease and some models thereof, less information is available in other brain regions that are also affected by synuclein pathology. Therefore, we sought to test the hypothesis that early α-synuclein pathology causes mitochondrial dysfunction and that this effect might be exacerbated in conditions of increased vulnerability in affected brain regions, such as the amygdala. We combined a model of intracerebral α-synuclein pathology seeding with chronic glucocorticoid treatment, which models non-motor symptoms of Parkinson’s disease and affects amygdala physiology. We measured mitochondrial respiration, ROS generation and protein abundance as well as α-synuclein pathology in male mice. Chronic corticosterone administration induced mitochondrial hyperactivity in the amygdala. Although injection of α-synuclein pre-formed fibrils into the striatum resulted in pronounced α-synuclein pathology in both striatum and amygdala, mitochondrial respiration in these brain regions was not compromised, regardless of corticosterone treatment. Our results suggest that early stage α-synuclein pathology does not influence mitochondrial respiration in the striatum and amygdala, even in corticosterone-induced respirational hyperactivity. We discuss our findings in light of relevant literature, warn of a potential publication bias and encourage scientists to report their negative results within the framework of this model