My ALS Adventure – What is ALS?

What is this malady of mine, Amyotrophic Lateral Sclerosis (ALS)?  I’ve researched it not to find a cure — none is known at this time — but so I don’t waste time on what cannot be a cure.

ALS is a progressive neurological disease in which motor neuron cells deteriorate and die.  Motor neurons send signals from the brain (upper motor neurons) via the spinal cord (lower motor neurons) to muscles throughout the body.

Motor neurons control all voluntary muscle movement including walking, talking, chewing and breathing.   As the signals they send grow weaker, the muscles they control waste away until at last the brain can no longer initiate and control voluntary movements.

Different groups of muscles are controlled by motor neurons in different parts of the brain (see illustration below).  About 70% of patients first develop symptoms in their arms or legs.  About 25% first notice speech or swallowing problems (bulbar onset) — I’m one of those — and about 5% start with symptoms in their trunk.

No matter where the first symptoms appear, the great majority of ALS patients end up losing function in all muscles.  We lose the ability to speak, eat, move, and even breathe.  Most of us die from respiratory failure, usually within 2 to 4 years, although about 10% of us survive for 10 or more years.

The literature says all ALS patients develop symptoms throughout their body but the chief neurologist I met at Lehigh, PA who has worked in the field the longest told me that’s not correct.  Some patients with bulbar onset ALS do not develop symptoms in other muscle groups.

Up to 10% of ALS patients inherit it from a parent via mutations in any one of over a dozen genes.  The remaining 90%, of which I am one, are believed to have a genetic predisposition to the disease that is activated by an environmental factor.

Genes are contained in chromosomes located mainly in the cell nucleus.  Every chromosome contains hundreds to thousands of genes and every human cell contains 23 pairs of chromosomes.  We have about 20,000 to 23,000 genes all told, around 400 random ones of which are, on average, defective in any one of us.

The entire structure and function of our body is governed by the proteins it synthesizes and that operation is controlled by genes.  Proteins are both building blocks for muscles, connective tissues, and other structures and they also, in the form of enzymes, carry out nearly all chemical processes within the body.  Our body produces thousands of different enzymes.

Our genetic system is highly complex.  Its operations incorporate error-correction mechanisms but it can go wrong with an enormous variety of results.  It amazes me it works at all!

How might errors (mutations) occur?  They can occur spontaneously.  When a cell divides, for example, it makes a copy of its DNA, the molecule that carries the genetic instructions controlling its operation.  Sometimes the copy is not quite perfect.  Environmental factors such as radiation, chemicals, bacteria and viruses can also cause DNA to break down and when it does, the cell may not repair it perfectly.

How does the body defend against environmental risks carried in the blood?  The walls of the blood vessels in the human brain are high-density cells that limit what substances can pass from the bloodstream to the brain more than the cell walls of capillaries do elsewhere in the body.

Severe inflammation such as I had in reaction to the Brown-tail Moths can temporarily weaken the bond between those cells making them a less effective barrier.

We know far more about how our genetic system works than we did even ten years ago but not yet enough.  Western medicine has no cure for ALS because its cause or causes are at this point still a mystery.  The only existing medication that slows its progression extends life by only a couple of months.  I take it.

Motor neurons are different from other cells because the genes that govern their operation are different.  Restoring their operation is not a matter of developing a drug to kill an external attacker such as a bacterium.  We’re not dealing with something that moves from one group of motor neurons to all others.  An environmental factor is triggering a change in our motor neurons’ genetic programming.

Curing ALS will require correcting the motor neurons’ genetic programming.  This December 10, 2017 report describes a potential approach based on CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), a naturally occurring bacterial defense system.

CRISPRs are repeating sequences of genetic code interrupted by “spacer” sequences – remnants of genetic code from past invaders.  The system of which they are part serves as a genetic memory that helps the cell detect and destroy invaders when they return.

CRISPRs can be programmed to target specific stretches of genetic code and edit DNA at precise locations, thus permanently modifying genes in living cells.  The first method to engineer CRISPR to edit the genome in mouse and human cells was published in January 2013.

In its current form, CRISPR isn’t technically gene therapy. Rather than replacing a diseased gene with a good one, it goes into the nucleus and directly cuts out faulty genes.

Meanwhile, since there is not yet a gene therapy for ALS, I am taking a treatment that has cured a significant number of MS patients and more recently, a number of ALS patients, too.  It is based on the idea that the body can, if treated in the right way, heal itself.

The treatment was developed by a doctor of Tibetan medicine who, earlier in his career, was sent by the Dalai Lama to reestablish Tibetan medicine in Mongolia and who is now based in San Diego, CA.  I am receiving this treatment from the first Westerner to qualify as a doctor of Tibetan medicine, a truly amazing achievement.  Her mentor is the Tibetan doctor who developed the treatment.

I will add comments to this post as I learn more about ALS.  I knew little about biology eighteen months ago and would be very grateful for comments by anyone who can correct or add to what I’ve learned so far.

My ALS Adventure – June 2016 to April 2017

I didn’t choose this as I did the experiences I learned so much from in business and trekking in the Himalayas but it is just as much of an adventure, a powerful opportunity for learning.

I hope my trip reports from this adventure will help others with ALS, those who care about them, and perhaps medical professionals.  The progression of symptoms is detailed enough to be useful to researchers.  How I have remained happy may be helpful to fellow patients.

These reports also benefit me in the same way as writing monthly status reports did in business.  They help me reflect.  It’s impossible from day to day to get an accurate sense of important changes that only become visible when you gain altitude.

This post tells how my symptoms progressed toward a diagnosis.  Next I’ll post about the nature of ALS.  Subsequent posts will be based on emails to family, friends and my doctor.

I’d prefer to write after I regain health as I did about depression.  There would then be no risk you’d be distracted by sympathy, but Western medicine has no cure for ALS.

I am receiving care from a wonderful Tibetan doctor who has cured other ALS patients but we can’t know if the treatment will work for me, which points to the overwhelming lesson from this journey — if I don’t write now, I may not have the chance to do so later.

So please, whatever is the most important thing you can do with your life, do it now.

Enough preamble.  Here’s what happened up until my ALS diagnosis nine months ago.

My symptoms began in mid-June 2016 when I was working under oak trees in Maine.  Their leaves were being eaten by Brown-tail Moth caterpillars to which many people are allergic.  An itchy rash developed on all my exposed skin and my tongue felt enlarged.

The rash was gone after two or three days but my speech was slightly slurred.  I could curl my tongue so it seemed I had not had a stroke.

My slurred speech was a bit worse after about three weeks, too long for an allergic reaction to be the explanation, so I went to my primary care doctor who ordered blood samples and a brain MRI.

The MRI showed no structural damage to my brain.   We got the blood test results by phone and were told they indicated tick-borne disease.  We didn’t think to ask which one and the doctor’s office could not locate the results later but I was put on a three week course of antibiotics.

At the end of the three weeks, July 26, about six weeks after the first symptoms, my speech was worse and my tongue felt weaker.

I was then examined by a neurologist.  She detected double vision when I look toward the upper left.  I wasn’t too surprised because I also get double vision if my head gets very cold in winter.  The neurologist ordered an ultrasound for blood flow on both sides of my neck

The ultrasound results were normal.  On August 16 the neurologist ordered more blood work.  Everything was fine except for my usual high cholesterol.  The results for tick-borne disease were negative.  She ordered an MRI for blood flow in my brain.

My brain blood flow was normal.  On August 30 the neurologist prescribed pyrostigm because my symptoms could result from ocular myesthenia.

The pyrostigm had no effect by September 7.  I had been doing very heavy physical work and driving 11+ hours back and forth between Maine and Pennsylvania so I wondered if the medication had not had the right conditions to be effective.

The neurologist said I must have had a stroke that left no trace in the structure of my brain.  She ordered a barium swallowing test which I took on September 16.  No problems were detected.

We moved to Gettysburg, PA and on November 3 I visited a new primary care doctor who prescribed speech therapy.

After three weeks of speech therapy that taught me to articulate more deliberately but left my tongue weaker and my speech worse as I tired, the therapist told me to stop the exercises and recommended consulting another neurologist.  The exercises would have been beneficial if I’d had a stroke so she believed it must be something else.

It was now early December, almost six months since the first symptoms.  My speech was continuing to deteriorate, swallowing was growing more difficult and my nostrils kept getting blocked.  We scheduled a consultation with a neurologist at Johns Hopkins Hospital but it would not be until March 1st.

I went to Nepal for Tibetan Buddhist teachings for six weeks right after New Year’s day.

By the time I returned in mid-February, eating had become a struggle.  It was hard for my tongue to maneuver food between my teeth, food was getting stuck in my cheeks, and it was hard to avoid biting my cheeks when I chewed.  There was no problem with jaw movement and I could swallow food without difficulty but I could take only small sips of liquid and I would sometimes gag which led to coughing fits.

On March 1, 2017 the Johns Hopkins neurologist said my symptoms indicated either Bulbar Myesthenia, Bulbar Myopathy or Lou Gehrig’s Disease (ALS).  She ordered an EMG with Nerve Conduction Study.

The EMG was performed by a different Johns Hopkins doctor, one who specializes in ALS, on March 22.  The sensory conduction showed reduced right ulnar sensory amplitude (the ulnar nerve runs from the neck to the hand and is our largest nerve unprotected by muscle or bone so injury is common), the motor conduction showed reduced velocity across the elbow segment of my right ulnar nerve, repetitive nerve stimulation was normal and needle EMG showed neurogenic changes limited to the right side of my tongue.  No weakness was detected anywhere else in my body.

Two days later (Mar 24) the first neurologist called to tell me the EMG ruled out Bulbar Myestenia and her colleague had diagnosed ALS.  She ordered a test of the strength of my diaphragm and a spinal tap that would include tests for Lyme Disease because Lyme can cross the blood-brain barrier when there is inflammation as there had been in my reaction to the Brown-tail Moth caterpillars.

On April 7 my speech was very indistinct after a week of very hard work outside.  I rested for a day and my speech was clearer the next day.  My tongue felt less weak but my lips were always weak so I dribbled.  I could still swallow food without difficulty but I hesitated with liquids.

I had the pulmonary test, spinal tap and a consultation with the ALS neurologist on April 10.  He said we had eliminated every other possibility so I definitely have ALS.  Weakness spreads to all muscles of most ALS patients and they die, usually from breathing problems, within a couple of years.

This is long enough for one post.  I’ll describe what happened next in future chapters.

It’s worth noting now, though, that in the eighteen months since my symptoms began, I have experienced no weakness in muscles other than my mouth and throat.  That means I may be one of those whose symptoms do not progress.