Additionally, cytokines may act on the vascular organ of the lamina terminalis, leading to the synthesis of prostaglandin (PG) E2 which acts on the hypothalamus, resulting in an increase in body temperature. Also, the release of cytokines and exogenous exotoxins coupled with an increase in intracranial pressure stimulate nociceptors in the meninges creating pain sensations. The release of cytotoxic molecules in the central nervous system results in extensive tissue damage and necrosis, such as damage to the olfactory nerve through lysis of nerve cells and demyelination. Specifically, the olfactory nerve and bulbs become necrotic and hemorrhagic. Spinal flexion leads to nuchal rigidity, or stiff neck, due to the stretching of the inflamed meninges. The increase in intracranial pressure stimulates the area postrema to create nausea sensations which may lead to brain herniation and damage to the reticular formation. Ultimately, the increase in cerebrospinal fluid from inflammation of the meninges increases intracranial pressure and leads to the destruction of the central nervous system. Although the exact pathophysiology behind the seizures caused by PAM is unknown, scientists speculate that the seizures arise from altered meningeal permeability caused by increased intracranial pressure. Pathogenesis
Naegleria fowleri propagates in warm, stagnant bodies of fresh water (typically during the summer months), and enters the central nervous system after insufflation of infected water by attaching itself to the olfactory nerve. It then migrates through the cribriform plate and into the olfactory bulbs of the forebrain, where it multiplies itself greatly by feeding on nerve tissue.
Naegleriasis (also known as primary amoebic meningoencephalitis; PAM) is an almost invariably fatal infection of the brain by the free-living unicellular eukaryote Naegleria fowleri. Symptoms are meningitis-like and include headache, fever, nausea, vomiting, a stiff neck, confusion, hallucinations and seizures. Symptoms progress rapidly over around five days, and death usually results within one to two weeks of symptoms.N. fowleri is typically found in warm bodies of fresh water, such as ponds, lakes, rivers and hot springs. It is also found in an amoeboid or temporary flagellate stage in soil, poorly maintained municipal water supplies, water heaters, near warm-water discharges of industrial plants and in poorly chlorinated or unchlorinated swimming pools. There is no evidence of it living in salt water. As the disease is rare, it is often not considered during diagnosis.Although infection occurs very rarely, it almost inevitably results in death. Of the 450 or so naegleriasis cases in the past 60 years, only seven have survived, for a case fatality rate of 98.5%. Signs and symptoms
Onset of symptoms begins one to nine days following exposure (with an average of five). Initial symptoms include changes in taste and smell, headache, fever, nausea, vomiting, back pain, and a stiff neck. Secondary symptoms are also meningitis-like including confusion, hallucinations, lack of attention, ataxia, cramp and seizures. After the start of symptoms, the disease progresses rapidly over three to seven days, with death usually occurring anywhere from seven to fourteen days later, although it can take longer.