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Post-malaria Neurological Syndrome - Types, Causes, Diagnosis, and Treatment

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Post-malaria neurological syndrome is a rare syndrome that affects individuals after recovering from malaria. To know more, read the article below.

Medically reviewed by

Dr. Prakashkumar P Bhatt

Published At September 5, 2022
Reviewed AtJanuary 10, 2024


Post-malaria neurological syndrome (PMNS) is characterized by neurological manifestations, including neurological deficit and encephalopathy. Cerebral malaria is a severe neurological condition after the individual has contracted malaria. This is seen one to four months after the disease condition. The disease mortality is high, and there is long-term neurocognitive impairment in some surviving victims. This article discusses the effects of the disease and the causes to understand neural defects and their treatment.

What Is Malaria?

A parasite is the cause of malaria, an illness spread by mosquitoes. Malaria patients frequently have chills, fever, and flu-like symptoms. If left untreated, they can die from serious consequences.


Malaria signs and indicators could include:

  • Chills with fever.

  • Overall unease.

  • Headache.

  • Vomiting and nausea.

  • Diarrhea.

  • Stomach ache.

  • Joint or muscle soreness.

  • Weary.

  • Breathing quickly.

  • Accelerated heart rate.

  • Cough.


A single-celled parasite belonging to the genus Plasmodium causes malaria. Mosquito bites are the most prevalent way for the parasite to infect humans.

  • Mosquitoes that are not contaminated. Feeding an individual with malaria gives a mosquito the infection.

  • Transmission of the parasite. One may contract malaria parasites if this mosquito bites again.

  • Within the hepatic organ. The parasites enter the liver after entering the body; some species can remain latent for up to a year.

  • The parasites infect the red blood cells in the vascular system once they have grown and exit the liver. Typically, symptoms of malaria appear at this time.

  • Moving on to the following individual. At this life cycle stage, if an uninfected mosquito bites a person, it will pick up malaria parasites and pass them on to other bite victims.

Other Means of Transmission: People can contract malaria by contracting contaminated blood since the parasites that cause the disease attack red blood cells. These include:

Risk Factors:

Those who are more susceptible to severe illnesses include:

  • Infants and young children.

  • Senior citizens.

  • Visitors from regions free of malaria.

  • Expectant mothers and their unborn offspring.

The issue is made worse in many nations with high malaria rates by a lack of information, medical care, and preventive measures.


Most often, one or more major complications from malaria result in deaths. These problems include:

  • Malaria in the Brain: In cerebral malaria, small blood arteries leading to the brain are blocked by parasite-filled blood cells, which can cause brain injury or edema. Seizures and comas can result from cerebral malaria.

  • Breathing Issues: Breathing difficulties may arise from pulmonary edema or accumulated lung fluid.

  • Organ Malfunction: Malaria can induce ruptures in the spleen, liver, or kidneys. Any of these ailments has the potential to be fatal.

  • Anemia: Anemia, or low red blood cell count, can be caused by malaria, resulting in insufficient oxygen delivery to the body's tissues.

  • Low Glucose Levels: Hypoglycemia, or low blood sugar, can be brought on by severe malaria infections or quinine, a frequent malaria medicine.


  • Shield the skin.

  • Apply skin-care insect repellent.

  • Put repellent on clothes.

  • Take a nap behind a net.

Where Is Post-Malaria Neurological Syndrome More Predominant?

Malaria is a disease that causes health issues that cause neurological symptoms, which leads to death in many tropical countries. Children below five years in the African race are more affected the most. Severe malaria is manifested as anemia. Some symptoms are hypoglycemia, seizure, acidosis, coma, and multiple organ failure.

What Are the Symptoms of PMNS?

Clinically, coma is the last stage of severe malaria infection.

Some other symptoms can be:

  • Seizure.

  • Progressive weakness.

  • Prostration.

  • Brain swelling.

  • Intracranial hypertension.

  • Retinal changes.

  • Abnormal breathing.

  • Multiorgan failure.

  • Body ache.

  • Fever.

  • Abdominal bleeding.

  • Pulmonary edema.

  • Cerebral venous.

  • Dural sinus thrombosis.

  • Some are also associated with bacterial infections.

What Are the Causes of Post-malaria Neurological Syndrome?

The mechanism of PMNS is not clearly understood, but an idea of how this neurological damage can be explained from the postmortem bodies.

  • Parasite Sequestration in the Brain: Parasite sequestration in cerebral microvasculature is the primary pathogenesis. This results in pathophysiological changes in cells and tissue and the sequestered parasites, which explains how the intravascular parasite can cause neural dysfunction. The parasite adheres to the endothelial surface using parasite-derived proteins exposed on the erythrocyte surface. This attaches to host receptors, which make intercellular adhesion. This causes brain necrosis and coma, as well as intracranial hypertension.

  • Cytokines, Chemokines, and Excitotoxicity: Cytokines and chemokines play a significant role in pathogenesis and have protective and harmful effects—parasite antigens released due to the multiplication of parasites this release both pro-and anti-inflammatory cytokines. Although the balance between these mediators is crucial for parasite control, their role in the pathogenesis of neuronal damage is unclear. Cytokine-mediated synaptic changes contribute to the syndrome of cerebral malaria. When this happens, it causes inflammation of brain cells and tissues, causing damage.

  • Epithelial injury, Apoptosis, BBB Dysfunction, and Intracranial Hypertension: These cause cytoadherence of pRBCs to the endothelium, which initiates a chain of events beginning with the transcription of genes involved in inflammation, cell-to-cell signaling, and signal communication, which result in endothelial activation, the release of Endothelial microparticles (EMPs), and apoptosis of host cells. There is widespread endothelial activation in vessels that contain pRBCs. Other complications of falciparum malaria, increases in circulating EMPs, are seen in patients in coma. Interactions between RBCs and platelets cause more damage to endothelial cells through a direct cytotoxic effect.

  • Cerebral Blood Flow and Perfusion: Patients with PMNS have an increased and profuse cerebral blood flow. This increases the probability of an adaptive response to the high metabolic necessity for oxygen and nutrient delivery. Reduced local perfusion is associated with abnormal electroretinography. Suppose the retina mirrors events in the brain. Likewise, a similar obstruction can be present. A coma in PMNS may result from under-perfusion in multiple but small areas of the brain because these patches of the tiny brain are affected. With early treatment and relief of obstruction, there is less tissue necrosis. Early restoration of perfusion can completely recover the gross neurological function in most patients. Therefore, this develops severe brain hypoxia, which leads to damage.

  • Seizures: Plasmodium falciparum is epileptogenic, increasing the risk and attacking parasitemia. Irreversible neural damage happens due to prolonged seizure activity; edema is recognized on MRI within days. Prolonged seizures may worsen this injury and create a vicious cycle of neural damage and more episodes.

  • Depth, Duration, and Cause of Coma: PMNS is not a single homogenous syndrome but rather four distinct groups: a prolonged state, covert status epilepticus, severe metabolic derangement, and a primary neurological syndrome. Patients with a long postictal condition can have coma secondary to seizures. The patients regain consciousness within six hours and have a good recovery. Patients with severe metabolic derangement regain consciousness a few hours after resuscitation. Impaired consciousness is a secondary phenomenon that is also common in this. Prolonged hypoglycemia or acidosis causes neuronal dysfunction or death. The outcome may depend on the duration of exposure among patients.

What Can Be Affected Due to PMNS?

  • Cognitive impairment.

  • Speech loss

  • Epilepsy.

  • Behavior and neuropsychiatric disorder.

What Are the Treatment and Management Options of PMNS?

  • Steroids.

  • Immunoglobulin.

  • Acetylsalicylic acid.

  • Heparin.

  • Anti-TNF agents.

  • Mannitol.

  • Iron chelation.

  • Micronutrients.

  • Prophylactic anticonvulsants are used for therapy.

  • Prophylactic Phenobarbital was associated with respiratory depression. The respiratory depressant prophylactic anticonvulsant, Fosphenytoin, and B5 complex provitamin pantethine prevented the development of post-malaria neurological syndrome.

  • Erythropoietin provides neuroprotection, infectious encephalopathy, and hypoxic-ischemic encephalopathy, which can also be reduced, and patients can have a better prognosis.


This is necessary for particular areas such as physical and occupational therapy, behavior and speech therapy, cognitive rehabilitation, and hearing aids. This can help the patient improve their condition and help to live a quality lifestyle.


Post-malaria neurological syndromes cause brain injury. Coma and brain damage develop through multiple mechanisms, and there are several reasons for brain injury. Therefore, combinations of adjuvant therapies are needed for specific mechanisms of brain injury to improve neurocognitive outcomes. Meanwhile, MRI can provide important insights into pathogenesis

Frequently Asked Questions


Can Malaria Cause Neurological Problems?

Yes, seizures, agitation, psychosis, impaired consciousness, and coma are among the neurological symptoms of malaria; the latter two symptoms are the hallmarks of cerebral malaria. The most serious neurological side effect of Plasmodium falciparum infection is cerebral malaria. After recovering from malaria, typically severe falciparum malaria, a rare self-limiting neurological complication known as a post-malaria neurological syndrome (PMNS), may develop. A wide range of neuropsychiatric manifestations characterizes it, from mild neurological deficit to severe encephalopathy.


Can Malaria Cause Permanent Damage to the Brain?

When malaria affects the brain, it becomes extremely dangerous. Plasmodium falciparum causes red blood cells to build up inside tiny blood vessels in the brain, obstructing blood flow and resulting in cerebral malaria. This may raise blood pressure and cause swelling in the brain, pushing sensitive brain tissue up against the skull. As a result, patients may experience seizures, fall into a coma, and, if they survive, experience permanent brain damage.


What Is the Treatment for Post-malaria Neurological Syndrome?

Treatment methods include using steroids, acetylsalicylic acid, immunoglobulin, Heparin, anti-TNF medications, Mannitol, micronutrients, iron chelation, and prophylactic anticonvulsants. Respiratory depression was linked to prophylactic phenobarbital. The post-malaria neurological syndrome was prevented by the respiratory depressant prophylactic anticonvulsant, Fosphenytoin, and the B5 complex provitamin pantethine.
Erythropoietin offers neuroprotection and can lessen the effects of infectious and hypoxic-ischemic encephalopathy and improve patient prognosis.


Can Malaria Stay in the Body Forever?

Some malaria parasite strains, which typically cause less severe disease, can linger for years and lead to relapses. Malaria has been known to remain in some people's blood for several decades if untreated. However, in general, the parasites are completely eradicated if you receive the proper treatment for the disease.


How Is Cerebral Malaria Diagnosed?

The asexual form of P. falciparum must be visible in thick and thin blood smears for diagnosing cerebral malaria. Before ruling out cerebral malaria, at least three smears must be negative. PCR (polymerase chain reaction) and the rapid diagnostic test (antigen detection test) could also be helpful. CSF (cerebrospinal fluid) analysis is required to rule out other possible causes of febrile encephalopathy. In cerebral malaria, the CSF is typically normal; however, a small pleocytosis (10–50 cells/mm3) and a protein elevation of up to 200 mg/dL may be present.


Is Cerebral Malaria Fatal?

Without treatment, cerebral malaria is always fatal. Parenteral antimalarials (Cinchonoids or artemisinin derivatives) are recommended for use in children, but even with this therapy, 15-20% of patients still pass away. However, mortality was reduced in adults who received intravenous artesunate therapy. Fortunately, a significant portion of those who do survive cerebral malaria typically make a full recovery and have all of their neurological symptoms go away. However, some neurological symptoms could linger for a few days or weeks after you recover from cerebral malaria.
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Dr. Prakashkumar P Bhatt
Dr. Prakashkumar P Bhatt



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