Physical, environmental, or direct chemical (drug) induced brain inflammation triggers general immune action toward endothelial linings of blood vessels in the brain. This process causes damage to the vessel wall and fibrinoid necrosis, narrowing the lumen due to thickening or total occlusion due to thrombosis resulting in tissue ischemia and necrosis. The inflammatory oxidative stress and lymphocytic action on the endothelial lumen can render rapid ischaemic or haemorrhagic changes commonly noted in radio-diagnostic reports as subcortical hyper or hypointense lesions depending on the nature of the impact on micro-vessels.

Haemorrhagic damage represents small vessel blood leakages while ischaemic changes will appear as T-1 weighed hyperintense infarcts in the brain. Ischaemic changes originate from endothelial scarring of micro-vessels (thrombosis) that eventually obstruct blood flow. These appear as chronic ischaemic hyperintensities.

Hyperintense lesions may also become demyelinatory and trigger excitotoxic neuroprotection at one point. This invites the action of GABA-induced neurotransmission inhibition. Not all microvascular neuroprotective transitions are MR visible depending on the scale of damage.

A similar immune endothelial action in cerebral venous sinuses prevents cerebrospinal outflow from the brain.

Inflammatory obstructions at micro-pores in venous sinuses are followed by a cerebrospinal fluid (CSF) pressure build-up.

The excessive CSF pressure begins to damage anterior forebrain structures such as the pituitary, hypothalamus, and pineal gland amongst other soft tissue. These changes are visible in MRI and often ignored by radiologists due to common occurrences.

At this stage of supratentorial damage, disoriented stimulation between the neuroendocrine glands begins to impact body chemistry and hormonal balance. Subjects experience sleep deprivation – insomnia, short-term memory loss – dementia, morning depression/anxiety, constant pain from head pressure, and a distinct ringing in their ears onsets. This condition in the ears is known as tinnitus and is sometimes accompanied by balance issues, and pain behind the ears. Lack of emotions – anhedonia or imagination – aphantasia amongst other HPT (hypothalamus-pituitary-thyroid) axis disorders such as hypothyroidism are also common in this category. A conflicting interaction between serotonin-cortisol and a damaged hypothalamus may also contribute to Akathisia in some subjects along with temperature sensitivity symptoms.

Primary therapeutic objectives require addressing immune modulation, endothelial regeneration, and neurogenesis.