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The Nature of the Beast


Begins on page 256 from In Search of Helen from Two Locks.

It’s all very complicated, but it helps to understand a bit about brain cells. There are two basic types, neurons and glia. Neurons get all the publicity. They’re the famous brain cells. We’ve each got about 100 billion, and each of those 100 billion can have thousands of connections to the others.


Neurons receive signals on dendrites, which sort of resemble tree branches connected to the cell body. Each neuron can have many dendrites coming in, but only one axon going out.


Axons can be quite long. The longest reaches from the bottom of our spines to our toes. What we typically call a nerve is actually a bundle of axons, sheathed in their own myelin, and wrapped together in layers of connective tissue.


Glia is derived from the Greek word for “glue.” For a long time, scientists thought the glial cells were there solely to support the neurons. Now they think there’s a lot more to it and that most likely both the neurons and glial cells are vital for proper brain communication.


Dr. Tamargo [at Johns Hopkins] reported “prominent degeneration of the white matter with gliosis and fragmented axons.” Gliosis refers to scarring in the central nervous system caused by brain trauma. Too much scarring leads to permanent damage.


So, Patsy had damaged myelin, damaged axons, and extensive scarring, adding up to a brain that could no longer send, receive, and process information in a way that would enable normal life.


Dr. Nadiu identified Patsy’s disease as one of the leukodystrophies, namely Hereditary Diffuse Leukoencephalopathy with Spheroids. Eventually, the people who decide these things, changed the name to “Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).”


In 2016, the European Journal of Neurology, the official journal of the European Academy of Neurology, published an extensive study of the disease based on 90 families and 120 cases.


According to the study, the disease “causes dementia, psychiatric symptoms, parkinsonism, seizures and other neurological symptoms, and typically begins when patients are in their 40s and 50s.”


They define psychiatric symptoms as “anxiety, depression, apathy, indifference, abulia, irritability, disinhibition, and distraction.” Neurologists use the term abulia to describe an absence of initiative, a lack of will.

Under motor dysfunction, the report talks of “parkinsonian symptoms, gait disturbances, spasticity,” and difficulty finding words or even speaking. They also mention dizziness, fatigue, and epilepsy, and point out that many patients, particularly younger women, and especially early on, are misdiagnosed with multiple sclerosis.


All of this sounds very familiar.


Dr. Nadiu was able to label the disease with confidence, but despite all the evidence indicating ALSP, she could not point to a specific gene to prove her diagnosis. The gene for ALSP wasn’t discovered until 2012.


The National Library of Medicine maintains a website called the Genetic Home Reference, which states that “leukoencephalopathy with neuroaxonal spheroids and pigmented glia” is “caused by mutations in the CSF1R gene.” CSF1R is short for colony stimulating factor 1 receptor, and according to the NIH website, “More than a dozen mutations in the CSF1R gene have been found in people with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).”


Which brings us briefly to the amazing and complicated topic of genes and chromosomes and deoxyribonucleic acid, which we all know as DNA. DNA is actually an amazingly complex molecule shaped like a very long twisted ladder and stuffed into the nucleus of every cell in every one of us and every other living thing.


The instructions for building each form of life and each member of each form are written in this molecule. Every living thing, from bacteria, algae, fungus, ants, Neanderthals, and elephants to humans develops from instructions written in the DNA. In humans, those instructions are passed down from parents, who got them from their parents, who got them from their parents, in these little packages called chromosomes.


We have 23 pairs of chromosomes. We get one of each chromosome from each parent for a total of 46 chromosomes. Each chromosome contains a distinct section of our total DNA, and within these sections our 20 to 25 thousand genes are defined. If you think of DNA as a language, each chromosome contains a library of books written in that language, and each gene is one of those books.


The CSF1R gene resides on the fifth chromosome. Helen got one of these chromosomes from Harry and one from Annie. Most likely, one of them contained the mutations that caused the disease.


It’s extremely complex how a cell reads and executes the instructions in its genes, but regardless of the amazing biochemical mechanics, each cell does get its instructions from the DNA in its nucleus and executes them. If something is wrong with the instructions, or if something is wrong in the execution of the instructions, terrible things can happen.

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