Neuropathology View of the lobes and major external structures of the human brain LENAS is seen with damage to the white matter and axons within the brain. The external human LENAS brain shows findings in several major structures. There is mild atrophy of the frontoparietal regions of the brain and a mild reduction of the thalamus and rostral (front) part of the caudate nucleus (which is located in an area of the brain called the basal ganglia). Abnormalities in the frontal, frontoparietal, and temporal lobes are most severe and predominant with LENAS and asymmetry of the cerebral hemispheres has sometimes been found. LENAS also may show moderately enlarged lateral ventricles and atrophy in corticospinal tracts as well as in the pons. The area where it is seen to be the most pronounced abnormalities appear in the white matter below the pre- and postcentral gyri that extend through the posterior limb of the internal capsule into pyramidal tracts of the brain stem. * The corpus callosum is variably affected. * Reactive astrocytes and macrophages are present, but no inflammation appears. * The cerebral cortex and basal ganglia are normal and contain no or only few<unk> . * Within the cerebellum, there is a marked loss of Purkinje cells seen but cerebral white matter is normal. leftSpecific Immunostains are used as the easiest identification of<unk><unk>  in LENAS which appear as round to oval shaped swellings and are seen in affected white matter. If there appears to be a large amount of loss in myelin sheaths on axons and these<unk> , LENAS progressed to become widespread. Electron Microscopy has also been used to identify<unk> . In LENAS, evidence of the<unk>  may show neurofilaments that are scattered amount electron-dense material and mitochondria. Subcortical U-fibers in the brain appear to be relatively spared, meaning they seem to not be involved in most cases but this does not mean they are not always/eventually involved. U-fibers represent connections which are between adjacent areas of the brain located within the cortex or deep in the white matter that are one of the last parts of the brain to be myelinated. In LENAS, it has been found that because these U-fibers are last to myelinate normally, they are also last to be affected as the disease progresses. Biochemistry The primary biochemical defect in LENAS disrupts normal states and may involve oxidative stress. Ceroids, which are essentially products of unsaturated fatty acids that build up, are found in macrophages and other glia is thought to be an end-product of oxidative damage, indicative of membrane damage from abnormal accumulation. The high levels of Iron is also present in LENAS which can be associated to cause an increased level of toxic free radicals and causing oxidative damage to the body, causing failure in our cellular energy systems. Disease Mechanism The mechanism of LENAS still seems to remain unclear and it varies as more research on this is being done. Some mechanisms that can be of clinical importance of why individuals show certain symptoms and which area of the brain has been shown to be consistent. Normally, the frontal lobe in our brain are important for our higher level executive functions. Predominance of white matter damage in this lobe has been found to be consistent with both the psychiatric and behavioral signs and symptoms pertaining to LENAS. The underlying symptoms seen of frontotemporal dementia seen commonly in LENAS is associated with the temporal lobe damage. There is a large disconnect in the brain between the lobes that reflect the neuropsychiatric symptoms that are common with the disease. Ataxia, which is related to our daily voluntary movements of muscles, are often present even in patients without cerebellar involvement which could reflect either minimal damage to the cerebellum or diffuse cerebral white matter lesions.
Leukoencephalopathy with neuroaxonal spheroids
Leukoencephalopathy with vanishing white matter
Megalencephalic leukoencephalopathy with subcortical cysts
Neurodegeneration with brain iron accumulation
Camel spongiform encephalopathy
Neurofibrillary tangle
Limbic-predominant age-related TDP-43 encephalopathy
Variably protease-sensitive prionopathy