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.
Ocular melanosis (OM) is a blue-gray and/or brown lesion of the conjunctiva that can be separated into benign conjunctival epithelial melanosis (BCEM) and primary acquired melanosis (PAM), of which the latter is considered a risk factor for uveal melanoma. The disease is caused by an increase of melanocytes in the iris, choroid, and surrounding structures. Overproduction of pigment by these cells can block the trabecular meshwork through which fluid drains from the eye. The increased fluid in the eye leads to increased pressure, which can lead to glaucoma. In humans, this is sometimes known as pigment dispersion syndrome. Benign Conjunctival Epithelial Melanosis
BCEM, also referred to as conjunctival hypermelanosis, complexion-associated melanosis, or racial melanosis, is a non-cancerous lesion of the conjunctiva that is more commonly found in dark-skinned individuals (over 90% of lesions are found in black persons and around 5% in white persons). It is due to excess production of melanin in the setting of a normal number of melanocytes in the conjunctiva. It appears very early in life and the pattern does not seem to change upon reaching adulthood. There can be asymmetrical involvement of the eyes, and lesions are usually described as flat, brown, and patchy areas of pigmentation. Primary Acquired Melanosis
PAM is a potentially cancerous lesion of the conjunctiva, which has a higher risk of transforming into a malignant melanoma in white persons. Nearly 75% of all melanomas that arise from the conjunctiva have been found to have occurred in the setting of PAM.