Brain temperature regulation in poor-grade subarachnoid hemorrhage patients – A multimodal neuromonitoring study

Elevated body temperature (T_core) is associated with poor outcome after subarachnoid hemorrhage (SAH). Brain temperature (T_brain) is usually higher than T_core. However, the implication of this difference (T_delta) remains unclear. We aimed to study factors associated with higher T_delta and its association with outcome. We included 46 SAH patients undergoing multimodal neuromonitoring, for a total of 7879 h of averaged data of T_core, T_brain, cerebral blood flow, cerebral perfusion pressure, intracranial pressure and cerebral metabolism (CMD). Three-months good functional outcome was defined as modified Rankin Scale ≤2. T_brain was tightly correlated with T_core (r = 0.948, p < 0.01), and was higher in 73.7% of neuromonitoring time (T_delta +0.18°C, IQR −0.01 – 0.37°C). A higher T_delta was associated with better metabolic state, indicated by lower CMD-glutamate (p = 0.003) and CMD-lactate (p < 0.001), and lower risk of mitochondrial dysfunction (MD) (OR = 0.2, p < 0.001). During MD, T_delta was significantly lower (0°C, IQR −0.2 – 0.1; p < 0.001). A higher T_delta was associated with improved outcome (OR = 7.7, p = 0.002). Our study suggests that T_brain is associated with brain metabolic activity and exceeds T_core when mitochondrial function is preserved. Further studies are needed to understand how T_delta may serve as a surrogate marker for brain function and predict clinical course and outcome after SAH.     

Matrix metalloproteinases and their tissue inhibitors (TIMPs) in Plasmodium falciparum malaria: serum levels of TIMP-1 are associated with disease severity

BACKGROUND: Molecular mechanisms involved in the pathogenesis of severe malaria caused by Plasmodium falciparum are not fully understood. Matrix metalloproteinases (MMPs) are enzymes that proteolytically degrade both the extracellular matrix and nonmatrix substances with various functions in the modulation of immune response. The key inhibitors of MMPs are the tissue inhibitors of metalloproteinases (TIMPs). METHODS: We studied levels of MMP-8, MMP-9, TIMP-1, and TIMP-2 on admission and after 24 h, using an enzyme-linked immunosorbent assay, in serum specimens from 50 Gabonese children with severe malaria, 43 children with uncomplicated malaria, and 27 healthy control children. RESULTS: Serum MMP-8 and TIMP-1 levels were significantly higher in the severe malaria and uncomplicated malaria groups, compared with those in the control group (P < .001). TIMP-1 levels were significantly higher in patients with severe malaria, compared with those in patients with uncomplicated malaria (P < .001). High TIMP-1 levels were significantly correlated with malaria severity, as determined by the simplified multiorgan dysfunction score (Spearman rank-correlation coefficient, 0.55; P < .001). CONCLUSIONS: TIMP-1 is associated with signs and symptoms of severe malaria. MMP-8 levels are elevated in patients with severe or uncomplicated P. falciparum malaria. MMPs and TIMPs may be relevant in the pathogenesis of severe malaria, either as proteolytic enzymes that degrade the extracellular matrix or as effectors and regulators of the immune response.     

Use of the multi-organ dysfunction score as a tool to discriminate different levels of severity in uncomplicated Plasmodium falciparum malaria

The usual criteria for severe malaria are not always sufficient to identify patients who subsequently develop this disease. The multi-organ dysfunction score (MODS) was assessed in 22 patients with uncomplicated Plasmodium falciparum malaria to test its usefulness in discriminating different severity levels. The MODS on admission was highly correlated with the baseline concentration of tumor necrosis factor--alpha (r = 0.83, P < 0.001) and the duration of symptoms after admission (r = 0.54, P = 0.01). The MODS was also correlated with parasite count (r = 0.52, P = 0.014), parasite clearance time (r = 0.54, P = 0.009), and fever clearance time (r = 0.58, P = 0.005). The above correlations remained significant after controlling for the initial parasitemia (P = 0.03 and 0.005). The MODS is simple and easy to apply and needs a recording time of less than three minutes. Thus, this score might provide a quantitative approach for determining severity in Plasmodium falciparum malaria.     

Risk Factors for Dysphagia and the Impact on Outcome After Spontaneous Subarachnoid Hemorrhage

Neurocritical Care - Despite the tremendous impact of swallowing disorders on outcome following ischemic stroke, little is known about the incidence of dysphagia after subarachnoid hemorrhage (SAH)...     

Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID): Study Design and Rationale

Neurocritical Care - As the COVID-19 pandemic developed, reports of neurological dysfunctions spanning the central and peripheral nervous systems have emerged. The spectrum of acute neurological...     

The Effect of Packed Red Blood Cell Transfusion on Cerebral Oxygenation and Metabolism After Subarachnoid Hemorrhage

Background

Anemia adversely affects cerebral oxygenation and metabolism after subarachnoid hemorrhage (SAH) and is also associated with poor outcome. There is limited evidence to support the use of packed red blood cell (PRBC) transfusion to optimize brain homeostasis after SAH. The aim of this study was to investigate the effect of transfusion on cerebral oxygenation and metabolism in patients with SAH.

Methods

This was a prospective observational study in a neurological intensive care unit of a university hospital. Nineteen transfusions were studied in 15 consecutive patients with SAH that underwent multimodality monitoring (intracranial pressure, brain tissue oxygen, and cerebral microdialysis). Data were collected at baseline and for 12 h after transfusion. The relationship between hemoglobin (Hb) change and lactate/pyruvate ratio (LPR) orbrain tissue oxygen (PbtO₂) was tested using univariate and multivariable analyses.

Results

PRBC transfusion was administered on the median post-bleed day 8. The average Hb concentration at baseline was 8.1 g/dL and increased by 2.2 g/dL after transfusion. PbtO₂ increased between hours 2 and 4 post-transfusion and this increase was maintained until hour 10. LPR did not change significantly during the 12-h monitoring period. After adjusting for SpO₂, cerebral perfusion pressure, and LPR, the change in Hb concentration was independently and positively associated with a change in PbtO₂ (adjusted b estimate = 1.39 [95 % confidence interval 0.09–2.69]; P = 0.04). No relationship between the change in Hb concentration and LPR was found.

Conclusions

PRBC transfusion resulted in PbtO₂ improvement without a clear effect on cerebral metabolism prior to SAH.

     

Neuroglucopenia and Metabolic Distress in Two Patients with Viral Meningoencephalitis: A Microdialysis Study

Background

Cerebral edema is a major cause of mortality following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Arginine vasopressin (AVP) and water channel aquaporin-4 (AQP4) have been implicated in the pathogenesis of CA-evoked cerebral edema. In this study, we examined if conivaptan, a V_1a and V₂ antagonist, attenuates cerebral edema following CA/CPR in wild type (WT) mice as well as mice with targeted disruption of the gene encoding α-syntrophin (α-syn^?/?) that demonstrate diminished perivascular AQP4 pool.

Methods

Isoflurane-anesthetized adult male WT C57Bl/6 and α-syn^?/? mice were subjected to 8 min CA/CPR and treated with either bolus IV injection (0.15 or 0.3 mg/kg) followed by continuous infusion of conivaptan (0.15 mg/kg/day or 0.3 mg/kg/day), or vehicle infusion for 48 h. Serum osmolality, regional brain water content, and blood–brain barrier (BBB) disruption were determined at the end of the experiment. Sham-operated mice in both strains served as controls.

Results

Treatment with conivaptan elevated serum osmolality in a dose-dependent manner. In WT mice, conivaptan at 0.3 mg dose significantly attenuated regional water content in the caudoputamen (81.0 ± 0.5 vs 82.5 ± 0.4 % in controls; mean ± SEM) and cortex (78.8 ± 0.2 vs 79.4 ± 0.2 % in controls), while conivaptan at 0.15 mg was not effective. In α-syn^?/? mice, conivaptan at 0.3 mg dose did not attenuate water content compared with controls. Conivaptan (0.3 mg/kg/day) attenuated post-CA BBB disruption at 48 h in WT mice but not in α-syn^?/? mice.

Conclusions

Continuous IV infusion of conivaptan attenuates cerebral edema and BBB disruption following CA. These effects of conivaptan that are dependent on the presence of perivascular pool of AQP4 appear be mediated via its dual effect on V₁ and V₂ receptors.

     

Tuberous sclerosis complex with unilateral perisylvian polymicrogyria and contralateral hippocampal sclerosis—A case report

Malformations of cortical development (MCD) encompass a wide spectrum of brain disorders. Although rare, the combination of certain MCD may occur.We report a rare case of combination of three distinct cerebral pathologies: tuberous sclerosis, polymicrogyria and hippocampal sclerosis in a patient with intractable epilepsy. Ictal EEG and ictal SPECT suggested right perisylvian area as a seizure onset zone. However, on MRI multiple potentially epileptogenic lesions were identified.The neurobiological background of the coexistence of different types of malformations of cortical development remains enigmatic.     

Apoptosis in experimental cerebral malaria: spatial profile of cleaved caspase-3 and ultrastructural alterations in different disease stages

Cerebral malaria (CM) is associated with high mortality and morbidity as a certain percentage of survivors suffers from persistent neurological sequelae. The mechanisms leading to death and functional impairments are yet not fully understood. This study investigated biochemical and morphological markers of apoptosis in the brains of mice infected with Plasmodium berghei ANKA. Cleaved caspase-3 was detected in the brains of animals with clinical signs of CM and immunoreactivity directly correlated with the clinical severity of the disease. Caudal parts of the brain showed more intense immunoreactivity for cleaved caspase-3. Double-labelling experiments revealed processing of caspase-3 primarily in neurons and oligodendrocytes. These cells also exhibited apoptotic-like morphological profiles in ultrastructural analysis. Further, cleavage of caspase-3 was found in endothelial cells. In contrast to neurons and oligodendrocytes, apoptosis of endothelial cells already occurred in early stages of the disease. Our results are the first to demonstrate processing of caspase-3 in different central nervous system cells of animals with CM. Apoptosis of endothelial cells may represent a critical issue for the development of the disease in the mouse model. Neurological signs and symptoms might be attributable, at least in part, to apoptotic degeneration of neurons and glia in advanced stages of murine CM.