Leukoencephalopathy with neuroaxonal spheroids
[2] The rarity and unknown prevalence of this disease may be due to most symptoms being similar to other common disorders, leading to misdiagnosis.
[6][3] White matter consists of nerve fibers (axons) covered by a substance called myelin that insulates and protects them.
This mutation changes protein receptors on the gene which normally plays a role in important cell signaling pathways; however, this altercation inhibits the regular function.
[7] Proteins in general attach (bind) to their specific receptor which "turns on" (activates) to stimulate a cascade of cellular signaling pathways crucial for cell function to occur.
The kinase domain, which is the region of CSF-1 receptor where the mutation occurs, is altered and thus the normal function that activates other proteins is compromised and cannot stimulate cell signaling pathways properly.
[5] 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.
[5] 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.
[5] Specific Immunostains are used as the easiest identification of neuroaxonal spheroids in LENAS which appear as round to oval shaped swellings and are seen in affected white matter.
[5] If there appears to be a large amount of loss in myelin sheaths on axons and these spheroids, LENAS progressed to become widespread.
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.
[10] 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.
As this disease is extremely rare, diagnosis is still very complex as many of these diagnostic criteria for LENAS can be mistaken for similar neurodegenerative disorders.
Social problems such as unemployment, divorce, financial troubles, and alcoholism as well as suicidal tendencies are often associated as this disease worsens over time.
[12] L-dopa or other dopaminergic therapies have not yet been beneficial in individuals with this disease but was noted that it may be worth trying as it does not show negative effects.
[12] Periodic clinical evaluation and surveillance to monitor the progression of the disease is appropriate to determine if changes need to be made: Because of how rare this genetic condition is an exact prognosis is still not known and varies.
[5] Some patients in this family rapidly developed severe dementia and died a few months after this onset whereas others had a more prolonged progression of the disease.
However, some current research has been done primarily on case studies in which scientists are attempting to find new mutations or new ways to diagnose.
[17] Most of the stem cells remain in the marrow until they are mature which then they are released for specific functions in the body such as carrying oxygen, providing infection protection, and helping blood clotting.
[17] A study done using hematopoietic stem cell therapy (HSCT) showed clinical benefit but suggested further exploration must be done.
[18] Findings using HSCT was beneficial in recessive disorders and saw that it may similarly enhance CSF1R signaling after partial loss seen in LENAS.
[18] In the subjects who had LENAS were introduced to HSCT and the finding of further progressed cells was minimal 15 years after the therapy was finished.
[18] The most important finding in the subject was that they retained a high level of communication and survived beyond 15 years after onset of symptoms.
This finding provides hope for future research direction and suggests that there may be great benefit to slow the progression of LENAS using HSCT.
