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(A) EEG recording showing widespread slow wave activity in association with opisthotonic posturing (onset indicated with an arrow). (B) EEG recorded 10 hours later. There is notable attenuation of electrical activity in the right parieto-temporal region (leads T4-C4, C4-Cz, T6-P4, P4-Pz). ICP (intracranial pressure), MAP (mean arterial pressure), and CPP (cerebral perfusion pressure) measured in mm Hg.
Source publication
Seizures are a prominent feature of childhood cerebral malaria, and are associated with an increased risk of death and neurological sequelae. We present the electroencephalographic (EEG) findings from a detailed clinical and electrophysiological study.
Children with cerebral malaria had EEGs recorded within six hours of admission, and at 12 hourly...
Contexts in source publication
Context 1
... intracranial pressures of below 20 mm Hg, fluctuations in ICP appeared to have no eVect on the background frequency of the EEG. EEG recording from one child with severe intracranial hypertension, however, showed widespread slow wave activity (fre- quencies of 0.5-1 Hz) in association with episodes of opisthotonic posturing, during which ICP rose to peaks of 30 to 40 mm Hg ( fig 1A). Within 10 hours, EEG showed attenuation of activity in the right temporo- parietal region ( fig 1B), and the right pupil became dilated with sluggish reaction to light. ...
Context 2
... recording from one child with severe intracranial hypertension, however, showed widespread slow wave activity (fre- quencies of 0.5-1 Hz) in association with episodes of opisthotonic posturing, during which ICP rose to peaks of 30 to 40 mm Hg ( fig 1A). Within 10 hours, EEG showed attenuation of activity in the right temporo- parietal region ( fig 1B), and the right pupil became dilated with sluggish reaction to light. Over the next five hours, despite regular doses of mannitol 0.5 g/kg, the ICP rose to above 80 mm Hg, the cerebral perfusion pressure fell below 30 mm Hg, and the entire EEG became flat and featureless. ...
Context 3
... it is particularly vulner- able to hypoxia when oxygen delivery to the brain is compromised as a result of sequestra- tion, severe anaemia, or inadequate cerebral perfusion caused by hypotension or raised intracranial pressure. 12 15 21 22 Because of their anatomical position close to the temporal lobes in the tentorial notch, the posterior cerebral arteries may be particularly vulnerable to com- promise in those patients who have acute intracranial hypertension and incipient tran- stentorial herniation, as illustrated by the EEGs in fig 1. Raised intracranial pressure, reduced cerebral perfusion pressure, and transtentorial herniation have been documented in cerebral malaria, 12 23 and in other paediatric encepha- lopathies. 24 By initiating the release of excito- toxic mediators such as glutamate or quinolinic acid, 25 local hypoxia may precipitate seizures, which, by raising intracranial pressure and increasing the demand for oxygen and glucose, may exacerbate the situation further. ...
Similar publications
Prolonged, multiple seizures complicate a high proportion of cases of childhood cerebral malaria, and several studies have shown an association between these and neurological sequelae. We prospectively studied 65 patients (38 female) admitted to Kilifi Hospital in 1994. Electroencephalographic recordings (EEGs) were made at 12-hourly intervals, wit...
Citations
... EEG may reveal a focal onset with secondary generalization. Rarely only electrographic seizures may be noted [39,40]. With disease progression, brainstem dysfunction may be noted, especially in children with abnormal pupillary and corneal reflexes, dysconjugate/ upward gaze, and irregular/stertorous breathing patterns. ...
... While hypoglycemia needs exclusion in such cases, more commonly, such abnormal body posturing suggests raised intracranial pressure. Extrapyramidal signs may develop during convalescence when a strong pout reflex and a brisk jaw-closing reflex may also be elicited [38,40]. In children with retinopathy, markedly increased brain volume, abnormal T2 signal intensity, and DWI abnormalities in the cortical, deep gray, and white matter structures had been noted [41••]. ...
Purpose of Review
To discuss the neurological complications and pathophysiology of organ damage following malaria infection.
Recent Findings
The principal advancement made in malaria research has been a better understanding of the pathogenesis of cerebral malaria (CM), the most dreaded neurological complication generally caused by Plasmodium falciparum infection. However, no definitive treatment has yet been evolved other than the use of antimalarial drugs and supportive care. The development of severe cerebral edema in CM results from two distinct pathophysiologic mechanisms. First, the development of “sticky” red blood cells (RBCs) leads to cytoadherence, where red blood cells (RBCs) get stuck to the endothelial walls and between themselves, resulting in clogging of the brain microvasculature with resultant hypoxemia and cerebral edema. In addition, the P. falciparum-infected erythrocyte membrane protein 1 (PfEMP1) molecules protrude from the raised knob structures on the RBCs walls and are in themselves made of a combination of human and parasite proteins in a tight complex. Antibodies to surfins, rifins, and stevors from the parasite are also located in the RBC membrane. On the human microvascular side, a range of molecules involved in host–parasite interactions, including CD36 and intracellular adhesion molecule 1, is activated during interaction with other molecules such as endothelial protein C receptor and thrombospondin. As a result, an inflammatory response occurs with the dysregulated release of cytokines (TNF, interleukins 1 and 10) which damage the blood–brain barrier (BBB), causing plasma leakage and brain edema. This second mechanism of CNS injury often involves multiple organs in adult patients in endemic areas but remains localized only to the central nervous system (CNS) among African children.
Summary
Neurological sequelae may follow both P. falciparum and P. vivax infections. The major brain pathology of CM is brain edema with diffuse brain swelling resulting from the combined effects of reduced perfusion and hypoxemia of cerebral neurons due to blockage of the microvasculature by parasitized RBCs as well as the neurotoxic effect of released cytokines from a hyper-acute immune host reaction. A plethora of additional neurological manifestations have been associated with malaria, including posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), malarial retinopathy, post-malarial neurological syndrome (PMNS), acute disseminated encephalomyelitis (ADEM), Guillain-Barré syndrome (GBS), and cerebellar ataxia. Lastly, the impact of the COVID-19 pandemic on worldwide malaria control programs and the possible threat from co-infections is briefly discussed.
... 9 Over 30% of paediatric CM survivors are estimated to develop neurodevelopmental sequelae detectable within 2 years of acute illness; for 10%-16% of survivors, these sequelae will include postmalaria epilepsy (PME). [10][11][12][13][14][15][16][17] Cerebral malaria (defined as coma and malaria parasitaemia, in absence other coma aetiology) 9 has been better studied than malaria that affects the CNS in general (manifested by alteration of consciousness or complicated seizures), yet the two conditions have been shown to have similar rates of neurodevelopmental sequelae. 10 16 18 Thus, any malaria infection affecting the CNS (CM) has high rates of ...
Introduction
Malaria affecting the central nervous system (CM) is a major contributor to paediatric epilepsy in resource-poor settings, with 10%–16% of survivors developing epilepsy within 2 years of infection. Despite high risk for post-malaria epilepsy (PME), biomarkers indicating which CM survivors will develop epilepsy are absent. Such biomarkers are essential to identify those at highest risk who might benefit most from close surveillance and/or preventive treatments. Electroencephalography (EEG) contains signals (specifically gamma frequency activity), which are correlated with higher risk of PME and provide a biomarker for the development of epilepsy. We propose to study the sensitivity of quantitative and qualitative EEG metrics in predicting PME, and the potential increased sensitivity of this measure with additional clinical metrics. Our goal is to develop a predictive PME index composed of EEG and clinical history metrics that are highly feasible to obtain in low-resourced regions.
Methods and analyses
This prospective observational study being conducted in Eastern Zambia will recruit 250 children aged 6 months to 11 years presenting with acute CM and follow them for two years. Children with pre-existing epilepsy diagnoses will be excluded. Outcome measures will include qualitative and quantitative analysis of routine EEG recordings, as well as clinical metrics in the acute and subacute period, including histidine-rich protein 2 levels of parasite burden, depth and length of coma, presence and severity of acute seizures, presence of hypoglycaemia, maximum temperature and 1-month post-CM neurodevelopmental assessment scores. We will test the performance of these EEG and clinical metrics in predicting development of epilepsy through multivariate logistic regression analyses.
Ethics and dissemination
This study has been approved by the Boston Children’s Hospital Institutional Review Board, University of Zambia Biomedical Research Ethics Committee, and National Health Research Authority of Zambia. Results will be disseminated locally in Zambia followed by publication in international, open access, peer-reviewed journals when feasible.
... In the attempt to further understand CM-associated epilepsy, EEG has been a powerful tool in investigation, treatment, and prognosis [51,52]. EEG findings during hospitalization predicted morbidity and mortality among of children with malaria [52]. ...
Purpose of the review
Neurocysticercosis (NCC) has been well recognized as a leading cause of epilepsy. More recently, studies of other parasitic diseases such as cerebral malaria (CM) and onchocerciasis are yielding novel insights into the pathogenesis of parasite-associated epilepsy. We compare the clinical and electrophysiological findings in epilepsy associated with these highly prevalent parasites and discuss the mechanisms involved in epileptogenesis.
Recent Findings
Electrophysiological and imaging biomarkers continue to emerge, and individuals who are at-risk of developing parasite-associated epilepsies are being identified with greater reliability. While both Taenia solium and Plasmodium falciparum directly affect the brain parenchyma, Onchocerca volvulus is not known to invade the central nervous system. Thus, the causal association between O. volvulus and epilepsy remains controversial.
Summary
Both NCC and CM have a well-defined acute phase when the parasites directly or indirectly invade the brain parenchyma and lead to local inflammatory changes. This is followed by a chronic phase marked by recurrent seizures. However, these stages of epileptogenic process have not been identified in the case of O. volvulus .
Graphical abstract
... The malaria control strategy adopted by the WHO for the years 2016-2030 is described on the concepts of the framework [ Figure 1], pillars and support elements. [3] Existing solutions There are several methods of diagnosing cerebral malaria: [7][8][9] • Computed tomography-scan • Electroencephalography (EEG) • Nuclear magnetic resonance imaging • Clinical analysis • Magnetoencephalography. ...
... The high spatial resolution of the EEG, its very affordable cost and the fact that it can play an important role in psychiatry, in particular in the classification between psychiatric and organic diseases among others, make the EEG one of the main diagnostic tools of clinical neurology. [8,10] The works of Crawley et al. [9] showed how the EEG is used to diagnose childhood cerebral malaria. Gwer et al. [11] described the EEG and clinical profile of seizures in children with non-traumatic coma, compared seizure detection by clinical observations with that by continuous EEG and related EEG features to the outcome. ...
Background:This work is a part of a new concept. The aim is to study the measurements that can be used as input to an
intelligent system for detecting cerebral malaria from an electroencephalogram (EEG).
Materials and Methods:The study of brain connectivity through the calculation of the phase lag index, which is an adjacency
matrix, allows evaluating the units such as degree, density and strength on each channel. These units were evaluated on
29 EEG recordings, consisting of twenty people suffering from coma and nine healthy individuals.
Results:Considering analysis of variance with two factors that are frequency band and group (patient and healthy control),
the degree and the density are always higher in healthy children compared to sick children. Nevertheless, the strength is
always higher in healthy children compared to sick children with the exception of the delta band on which the values are
equal and the alpha band on which the strength is higher in sick children by the report to healthy children.
Conclusion:There is a significant difference (P = 0.002) between the strength of sick people compared to healthy people.
Such technology could help reduce the death rate from malaria, in general, and cerebral malaria, in particular, especially in
sub‑Saharan Africa where this rate is very high..
... The malaria control strategy adopted by the WHO for the years 2016-2030 is described on the concepts of the framework [ Figure 1], pillars and support elements. [3] Existing solutions There are several methods of diagnosing cerebral malaria: [7][8][9] • Computed tomography-scan • Electroencephalography (EEG) • Nuclear magnetic resonance imaging • Clinical analysis • Magnetoencephalography. ...
... The high spatial resolution of the EEG, its very affordable cost and the fact that it can play an important role in psychiatry, in particular in the classification between psychiatric and organic diseases among others, make the EEG one of the main diagnostic tools of clinical neurology. [8,10] The works of Crawley et al. [9] showed how the EEG is used to diagnose childhood cerebral malaria. Gwer et al. [11] described the EEG and clinical profile of seizures in children with non-traumatic coma, compared seizure detection by clinical observations with that by continuous EEG and related EEG features to the outcome. ...
Background: This work is a part of a new concept. The aim is to study the measurements that can be used as input to an
intelligent system for detecting cerebral malaria from an electroencephalogram (EEG).
Materials and Methods: The study of brain connectivity through the calculation of the phase lag index, which is an adjacency
matrix, allows evaluating the units such as degree, density and strength on each channel. These units were evaluated on
29 EEG recordings, consisting of twenty people suffering from coma and nine healthy individuals.
Results: Considering analysis of variance with two factors that are frequency band and group (patient and healthy control),
the degree and the density are always higher in healthy children compared to sick children. Nevertheless, the strength is
always higher in healthy children compared to sick children with the exception of the delta band on which the values are
equal and the alpha band on which the strength is higher in sick children by the report to healthy children.
Conclusion: There is a significant difference (P = 0.002) between the strength of sick people compared to healthy people.
Such technology could help reduce the death rate from malaria, in general, and cerebral malaria, in particular, especially in
sub‑Saharan Africa where this rate is very high.
... CM has predominant central nervous system (CNS) clinical findings including encephalopathy, seizures and increased brain volume; this latter feature is strongly associated with death [12][13][14][15]. CNS autopsies in CM demonstrate microvascular occlusion and haemorrhages in the brain microvasculature due to parasite adherence, with accompanying neuronal degeneration [16][17][18][19]. ...
Background:
Cerebral malaria (CM) is associated with morbidity and mortality despite the use of potent anti-malarial agents. Brain endothelial cell activation and dysfunction from oxidative and inflammatory host responses and products released by Plasmodium falciparum-infected erythrocytes (IE), are likely the major contributors to the encephalopathy, seizures, and brain swelling that are associated with CM. The development of adjunctive therapy to reduce the pathological consequences of host response pathways could improve outcomes. A potentially protective role of the nuclear factor E2-related factor 2 (NRF2) pathway, which serves as a therapeutic target in brain microvascular diseases and central nervous system (CNS) inflammatory diseases such as multiple sclerosis was tested to protect endothelial cells in an in vitro culture system subjected to tumour necrosis factor (TNF) or infected red blood cell exposure. NRF2 is a transcription factor that mediates anti-oxidant and anti-inflammatory responses.
Methods:
To accurately reflect clinically relevant parasite biology a unique panel of parasite isolates derived from patients with stringently defined CM was developed. The effect of TNF and these parasite lines on primary human brain microvascular endothelial cell (HBMVEC) activation in an in vitro co-culture model was tested. HBMVEC activation was measured by cellular release of IL6 and nuclear translocation of NFκB. The transcriptional and functional effects of dimethyl fumarate (DMF), an FDA approved drug which induces the NRF2 pathway, on host and parasite induced HBMVEC activation was characterized. In addition, the effect of DMF on parasite binding to TNF stimulated HBMVEC in a semi-static binding assay was examined.
Results:
Transcriptional profiling demonstrates that DMF upregulates the NRF2-Mediated Oxidative Stress Response, ErbB4 Signaling Pathway, Peroxisome Proliferator-activated Receptor (PPAR) Signaling and downregulates iNOS Signaling and the Neuroinflammation Signaling Pathway on TNF activated HBMVEC. The parasite lines derived from eight paediatric CM patients demonstrated increased binding to TNF activated HBMVEC and varied in their binding and activation of HBMVEC. Overall DMF reduced both TNF and CM derived parasite activation of HBMVEC.
Conclusions:
These findings provide evidence that targeting the NRF2 pathway in TNF and parasite activated HBMVEC mediates multiple protective pathways and may represent a novel adjunctive therapy to improve infection outcomes in CM.
... Yet studies of EEG in CM have to date been by visual inspection, and have not revealed any relationships between conventional EEG findings (e.g. interictal abnormalities, background slowing) and likelihood of post-CM epilepsy [11,18,19]. Accordingly, knowledge if digital EEG analysis, specifically spectral analysis of relative power in specific EEG frequency, can improve post-CM epilepsy prediction remains unknown. ...
... EEG spectral analysis was performed using Persyst Software (version 13, Rev.E2, 2019.10.08). Raw time series EEG data were converted to frequency domain using FFT in 1 Hz frequency bins over 8-s time windows and power across the 1-60 Hz range in delta (1-4 Hz), theta (5-7 Hz), alpha (8-12 Hz), beta (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), and gamma (30-60 Hz) frequency bands were initially analyzed. These initial analyses demonstrated that only power in the delta and gamma frequency bands differed significantly between the CM with epilepsy (CM+Epi) and CM without epilepsy (CMÀEpi) groups; therefore, subsequent analyses were only focused on power within these bands. ...
... Our study expands upon the use of standard EEG recordings obtained from CM survivors and demonstrates the utility of spectral analyses in predicting post-CM epileptogenesis. Prior studies have described conventional EEG metrics in CM as they relate to adverse outcomes, specifically mortality [18,19,38]. Diffuse background slowing, lower amplitude activity, poor reactivity and state change, asymmetry or focal slowing, and epileptiform features have all been reported in this population, which is a reflection of the acute illness. ...
Objective
Cerebral malaria (CM) affects 500,000 million children annually, 10% whom develop epilepsy within two years. Acute identification of biomarkers for post-CM epilepsy would allow for follow-up of the highest risk populations in resource-limited regions. We investigated the utility of electroencephalogram (EEG) and clinical metrics obtained during acute CM infection for predicting epilepsy.
Methods
We analyzed 70 EEGs recorded within 24 h of admission for CM hospitalization obtained during the Blantyre Malaria Project Epilepsy Study (2005–2007), a prospective cohort study of pediatric CM survivors. While all studies underwent spectral analyses for comparisons of mean power band frequencies, a subset of EEGs from the 10 subjects who developed epilepsy and 10 age- and sex-matched controls underwent conventional visual analysis. Findings were tested for relationships to epilepsy outcomes.
Results
Ten of the 70 subjects developed epilepsy. There were no significant differences between groups that were analyzed via visual EEG review; however, spectral EEG analyses revealed a significantly higher gamma-delta power ratio in CM survivors who developed epilepsy (0.23 ± 0.10) than in those who did not (0.16 ± 0.06), p = 0.003. Excluding potential confounders, multivariable logistic-regression analyses found relative gamma power (p = 0.003) and maximum temperature during admission (p = 0.03) significant and independent predictors of post-CM epilepsy, with area under receiver operating characteristics (AUROC) curve of 0.854.
Conclusions
We found that clinical and EEG metrics acquired during acute CM presentation confer risk of post-CM epilepsy. Further studies are required to investigate the utility of gamma activity as a potential biomarker of epileptogenesis and study this process over time. Additionally, resource limitations currently prevent follow-up of all CM cases to surveil for epilepsy, and identification of acute biomarkers in this population would offer the opportunity to allocate resources more efficiently.
... Seizures, a common complication, are also a risk factor for post-CM brain injury [2,5]. CM-associated seizures are prolonged, repetitive, focal, and refractory with subclinical seizures occurring in 18-47% [2,6,7]. Seizure management is challenging because phenobarbital and benzodiazepines remain the primary treatments, respiratory suppression is a common complication of both medications, and ventilatory support is generally unavailable [8]. ...
Background:
Acute seizures are common in pediatric cerebral malaria (CM), but usual care with phenobarbital risks respiratory suppression. We undertook studies of enteral levetiracetam (eLVT) to evaluate pharmacokinetics (PK), safety and efficacy including an open-label, randomized controlled trial (RCT) comparing eLVT to phenobarbital.
Methods:
Children 24-83 months old with CM were enrolled in an eLVT dose-finding study starting with standard dose (40 mg/kg load, then 30 mg/kg Q12 hours) titrated upward until seizure freedom was attained in 75% of subjects. The RCT that followed randomized children to eLVT vs. phenobarbital for acute seizures and compared the groups on minutes with seizures based upon continuous electroencephalogram. Due to safety concerns, midway through the study children allocated to phenobarbital received the drug only if they continued to have seizures (either clinically or electrographically) after benzodiazepine treatment. Secondary outcomes were treatment failure requiring cross over, coma duration and neurologic sequelae at discharge. PK and safety assessments were also undertaken.
Results:
Among 30 comatose CM children, eLVT was rapidly absorbed and well-tolerated. eLVT clearance was lower in patients with higher admission serum creatinine (SCr), but overall PK parameters were similar to prior pediatric PK studies. Within 4 h of the first dose, 90% reached therapeutic levels (> 20 μg/mL) and all were above 6 μg/mL. 7/7 children achieved seizure freedom on the initial eLVT dose. Comparing 23 eLVT to 21 phenobarbital patients among whom 15/21 received phenobarbital, no differences were seen for minutes with seizure, seizure freedom, coma duration, neurologic sequelae or death, but eLVT was safer (p = 0.019). Phenobarbital was discontinued in 3/15 due to respiratory side effects.
Conclusion:
Enteral LVT offers an affordable option for seizure control in pediatric CM and is safer than phenobarbital.
Trial registration:
NCT01660672 . NCT01982812 .
... EEG is not routinely available across Africa. Previously published single-site case series have reported a number of abnormalities in the EEGs of children with CM including diffuse slowing, atypical sleep elements (spindles and vertex waves), and epileptiform activity [5,10,11]. In a case series of 65 Kenyan children with CM, a slower background frequency was significantly associated with an increased risk of death [5]. ...
... Previously published single-site case series have reported a number of abnormalities in the EEGs of children with CM including diffuse slowing, atypical sleep elements (spindles and vertex waves), and epileptiform activity [5,10,11]. In a case series of 65 Kenyan children with CM, a slower background frequency was significantly associated with an increased risk of death [5]. Burst-suppression was found in a higher proportion of children who died compared to those who lived, but the numbers of children with burst-suppression was small and the differences in proportions between outcome groups were not statistically significantly different. ...
Background:
Electroencephalography at hospital presentation may offer important insights regarding prognosis that can inform understanding of cerebral malaria (CM) pathophysiology and potentially guide patient selection and risk stratification for future clinical trials. Electroencephalogram (EEG) findings in children with CM in Uganda and Malawi were compared and associations between admission EEG findings and outcome across this diverse population were assessed. Demographic, clinical and admission EEG data from Ugandan and Malawian children admitted from 2009 to 2012 with CM were gathered, and survivors assessed for neurological abnormalities at discharge.
Results:
281 children were enrolled (Uganda n = 122, Malawi n = 159). The Malawian population was comprised only of retinopathy positive children (versus 72.5% retinopathy positive in Uganda) and were older (4.2 versus 3.7 years; p = 0.046), had a higher HIV prevalence (9.0 versus 2.8%; p = 0.042), and worse hyperlactataemia (7.4 versus 5.2 mmol/L; p < 0.001) on admission compared to the Ugandan children. EEG findings differed between the two groups in terms of average voltage and frequencies, reactivity, asymmetry, and the presence/absence of sleep architecture. In univariate analyses pooling EEG and outcomes data for both sites, higher average and maximum voltages, faster dominant frequencies, and retained reactivity were associated with survival (all p < 0.05). Focal slowing was associated with death (OR 2.93; 95% CI 1.77-7.30) and a lower average voltage was associated with neurological morbidity in survivors (p = 0.0032).
Conclusions:
Despite substantial demographic and clinical heterogeneity between subjects in Malawi and Uganda as well as different EEG readers at each site, EEG findings on admission predicted mortality and morbidity. For CM clinical trials aimed at decreasing mortality or morbidity, EEG may be valuable for risk stratification and/or subject selection.
... Cerebral malaria (CM) is one of the major complication of Plasmodium falciparum infection and even with optimal anti-malarial treatment, more than 25% of cases result in death or cognitive and visual impairment [1][2][3]. A pathophysiological symptom associated to CM is the convulsive status epilepticus, characterized by constant seizures crisis [4]. ...
Background
Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has usually been associated with cognitive, behavioural and motor dysfunctions, being the retinopathy the most serious consequence resulting from the disease. The pathophysiological mechanisms underlying this complication remain incompletely understood. Several experimental models of CM have already been developed in order to clarify those mechanisms related to this syndrome. In this context, the present work has been performed to investigate which possible electrophysiological and neurochemistry alterations could be involved in the CM pathology.
Methods
Experimental CM was induced in Plasmodium berghei-infected male and female C57Bl/6 mice. The survival and neurological symptoms of CM were registered. Brains and retina were assayed for TNF levels and NOS2 expression. Electroretinography measurements were recorded to assessed a- and b-wave amplitudes and neurochemicals changes were evaluated by determination of glutamate and glutathione levels by HPLC.
Results
Susceptible C57Bl/6 mice infected with ≈ 10⁶ parasitized red blood cells (P. berghei ANKA strain), showed a low parasitaemia, with evident clinical signs as: respiratory failure, ataxia, hemiplegia, and coma followed by animal death. In parallel to the clinical characterization of CM, the retinal electrophysiological analysis showed an intense decrease of a- and-b-wave amplitude associated to cone photoreceptor response only at the 7 days post-infection. Neurochemical results demonstrated that the disease led to a decrease in the glutathione levels with 2 days post inoculation. It was also demonstrated that the increase in the glutathione levels during the infection was followed by the increase in the ³H-glutamate uptake rate (4 and 7 days post-infection), suggesting that CM condition causes an up-regulation of the transporters systems. Furthermore, these findings also highlighted that the electrophysiological and neurochemical alterations occurs in a manner independent on the establishment of an inflammatory response, once tumour necrosis factor levels and inducible nitric oxide synthase expression were altered only in the cerebral tissue but not in the retina.
Conclusions
In summary, these findings indicate for the first time that CM induces neurochemical and electrophysiological impairment in the mice retinal tissue, in a TNF-independent manner.
