Overview
The World Health Organization (WHO) defines brain malaria as a severe form of P. falciparum malaria that involves cerebral symptoms. Patients with Brain Malaria or Cerebral Malaria, after experiencing a seizure, usually fall into a coma that lasts for more than 30 minutes. Thus patients who show any evidence of brain dysfunction or altered consciousness should be treated for severe malaria.
The most severe neurological consequence of Plasmodium falciparum malaria infection is cerebral malaria. About 1% of children infected with P. falciparum may develop cerebral malaria, with extremely low prevalence in adults. On the other hand, cerebral malaria is more likely in older children and adults in low-transmission areas. The mortality rate in cerebral malaria is substantial, and some survivors suffer brain injuries that result in long-term neurocognitive deficits.
Introduction
Malaria is a deadly and one of the most common infectious diseases across the globe. Cerebral malaria (CM) or Brain malaria is a potentially reversible encephalopathy caused by P. falciparum. It is essential to understand that any cerebral disease present in a person cannot be called Brain malaria or Cerebral Malaria. The primary criterion that defines Cerebral Malaria includes:
- The patient shows the presence of the asexual form of P. falciparum in the blood smear.
- Patients with malaria are in a coma due to other reasons like encephalitis, encephalopathies, toxicity, trauma, etc.
- Glasgow scale <11/14 in adults and the Blantyre scale <2 in children
Epidemiology
In tropical nations, falciparum malaria is a leading cause of illness, neuro disability, and mortality. Even though 40% of the world’s population is at risk, most transmission happens in Sub-Saharan Africa. Young children under the age of five are getting affected, and the disease’s incidence falls with increased immunity in older children. Malaria is more common among adults in Southeast Asia, but the clinical characteristics are distinct. There are around 500 million clinical cases per year. Approximately one percent of symptomatic infections might progress to severe malaria.
Anemia, hypoglycemia, metabolic acidosis, frequent seizures, coma, or multiple organ failure are symptoms of severe malaria, which many believe in killing over one million people each year. However, the most severe neurological symptom of acute malaria is cerebral malaria. Children in endemic areas of Africa suffer the brunt of the disease, with an annual incidence of 1,120/100,000/year. Pre-school children have the highest frequency, with an estimated 575,000 children in Africa contracting cerebral malaria each year. Recent data, on the other hand, imply that severe malaria is on the decline.
Symptoms
The symptoms of cerebral malaria appear 10 to 15 days after the bite of the female anopheles mosquito. Patients often arrive with high fever, headache, myalgia, sweating, drowsiness, delirium, agitation, and other flu-like symptoms. In a later stage, these symptoms lead to coma. Thus, the defining symptom of cerebral malaria is coma. However, the onset of this neurological complication can be rapid or delayed. Thus, patients showing up with the above symptoms should be monitored carefully.
In patients with suppressed immunity due to any existing disease and children, the manifestation of cerebral malaria can occur in the first six to twelve hours. The reported manifestations in the above category of patients include nausea, vomiting, abdominal pain, tachycardia, arthralgias, and hepatosplenomegaly.
The following symptoms are commonly found in patients with cerebral malaria:
- Open-eyed
- Electroencephalographic abnormalities ( abnormal EEG report)
- Dysconjugate gaze ( The eyes fail to turn together in the same direction)
- Abnormal posturing
- Decorticate rigidity (abnormal posture where the patient has bent arms, clenched fists, and leg held out straight.)
- Decerebrate rigidity ( caused due to midbrain lesion)
- Neck rigidity (Discomfort in the neck while looking back or turning the head from side to side.)
- Opisthotonos (Muscle spasms that lead to backward arching of the head, neck, and spine.)
- Seizures
- Sustained ocular deviation, usually upward or lateral
- Nystagmus ( An ocular condition in which the eyes make repetitive, uncontrolled movements)
Fixed jaw closure and tooth chewing are two other symptoms that are common indications of cerebral malaria. Non-neurological symptoms associated with cerebral malaria include:
- liver and spleen enlargement
- jaundice
- pulmonary edema
- renal failure
- Pallor
- Hypoglycemia
- Bleeding
- Hypotension
- Severe anemia.
Malignant retinopathy is another significant consequence of cerebral malaria that can distinguish it from other encephalopathies found in malaria-endemic areas.
Malignant retinopathy in malaria is caused by the cerebral sequestration of parasites in the brain, and it can be diagnosed by looking for four primary symptoms:
- Whitening of the retina
- Changes in the vessel
- Papilledema
- Retinal hemorrhages
In children with cerebral malaria, intracranial pressure increases frequently, and deaths associated with different herniation syndromes have been reported. Symptoms of broad CNS involvement in children with CM include:
- Generalised tonic-clonic convulsions.
- Focal seizures.
- Posturing.
- Conjugate gaze deviations.
- Respiratory rhythm abnormalities (including Cheyne–Stokes respirations).
Patients who survive have a reasonably quick recovery; most children who survive cerebral malaria episodes regain full consciousness within 48 hours.
Risk Factors for Brain Malaria
Since cerebral malaria is an outcome of severe malaria, thus the risk factors are similar to malaria to some extent. The risk factors for cerebral malaria include:
- The presence of garbage and stagnant water near the house or inside the house acts as a breeding place for the mosquito.
- Traveling to malaria-infected regions without proper precautions like mosquito repellent cream, mosquito nets, full-length dress, etc.
- People not wearing a full-length dress while going out of their house
- People not using mosquito nets while sleeping
- Low utilization of indoor residual spray and improper lightning in the house during the daytime.
- Lack of knowledge about malaria
Cerebral malaria leads to persisting impairment of the cognitive and neurological functions of the human brain. A study published online in 2005 in the journal Archives of Disease in Childhood found the following risk factors responsible for impairment of the cognitive and neurological functions of the human brain in children (6-9 years) with cerebral malaria:
- Multiple seizures
- Deep/Prolonged Coma
- Hypoglycemia
- Severe Malnutrition
- Clinical symptoms of intracranial hypertension
Major pre-existing health complications that are risk factors and are considered to lead the pathogenesis of coma in patients with cerebral malaria includes:
- Hypovolemia
- Hypoglycemia
- Hyperpyrexia
- Bleeding Disorders
- Lactic Acidosis
- Anemia
- Pulmonary Edema
Treatment
Antimalarial medications can be divided into two categories: Artemisinin derivatives and Cinconcha alkaloids-derived drugs. Artemisinin derivatives include artesunate and artemether, whereas the latter include quinine and quinidine. Quinine is the preferred treatment for cerebral malaria. Because severe malaria tends to affect multiple organ systems; thus additional medical procedures are required to manage the consequences. Cerebral Malaria patients in coma should be intubated and, if necessary, ventilated artificially. In addition, because seizures are a common complication of cerebral malaria, medical treatment with anticonvulsants is essential.
Conclusion
The most severe neurological consequence of Plasmodium falciparum infection is cerebral malaria. Children in Sub-Saharan Africa are the most afflicted, with about 575,000 cases per year. Patients who survive cerebral malaria have a higher risk of neurological and cognitive abnormalities, behavioral problems, and epilepsy, making cerebral malaria a prominent cause of childhood neuro disability in the region. The pathophysiology of neurocognitive sequelae in cerebral malaria is poorly understood. Coma can develop through various pathways, and brain injury can occur through a variety of mechanisms. The mechanism by which an intravascular parasite produces such brain damage is unknown. Research is in progress on the life cycle of P.falciparum. Better treatment and management practices that will reduce mortality in cerebral malaria will show up soon.
References
- Idro, R., Marsh, K., John, C. C., & Newton, C. R. (2010). Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatric research, 68(4), 267–274. https://doi.org/10.1203/PDR.0b013e3181eee738
- Cerebral Malaria. Accessed at
https://www.sciencedirect.com/topics/medicine-and-dentistry/cerebral-malaria - Cuffari, Benedette. (2021, August 17). What is Cerebral Malaria?. News-Medical. Retrieved on October 27, 2021 from https://www.news-medical.net/health/What-is-Cerebral-Malaria.aspx.
- Tesfahunegn, A., Berhe, G., & Gebregziabher, E. (2019). Risk factors associated with malaria outbreak in Laelay Adyabo district northern Ethiopia, 2017: case-control study design. BMC public health, 19(1), 484. https://doi.org/10.1186/s12889-019-6798-x
- Idro, R., Carter, J. A., Fegan, G., Neville, B. G., & Newton, C. R. (2006). Risk factors for persisting neurological and cognitive impairments following cerebral malaria. Archives of disease in childhood, 91(2), 142–148. https://doi.org/10.1136/adc.2005.077784
- Valentim M. Cerebral malaria. J Neurol Stroke. 2018;8(4):216-221. DOI: 10.15406/jnsk.2018.08.00313
