APNARCOPLEXIC

What is a Rare Disease?

In the U.S., any disease affecting fewer than 200,000 people is considered rare. This definition comes from the Orphan Drug Act of 1983 and is slightly different from the definition used in Europe. There are nearly 7,000 rare diseases affecting nearly 30 million Americans. In other words, almost one in ten Americans are suffering from rare diseases.

Besides dealing with their specific medical problems, people with rare diseases struggle to get a proper diagnosis, find information, and get treatment. The rarity of their conditions makes medical research more difficult.

Oh yeah…this is every year on the last day of February…not just Leap Year’s! Perhaps I should shift my advocacy focus to something along these lines, since I have been diagnosed with two rare disease, since I blogged about “RARE Disease Day 2012″.

First is Narcolepsy, which I’ve had symptoms that could be argued trace back to late Elementary/Early High School (which got missed, since teachers were on strike for most of that year.) Though didn’t really become a significant problem to me, personally, until sometime during Freshman year at University (where, I had come across a clipping that there were pockets of H1N1 cases reported for the ‘86/’87 flu season.)

I received my second/current diagnosis of Narcolepsy in July 2012.

The first one in 2011 was based on Neurologist re-review of MSLT, but then he reversed his diagnosis for Narcolepsy on the basis that my Cataplexy wasn’t of the severe kind, and by spinal tap.

DSM-5 says narcolepsy is periods of an irresistible desire to sleep, or to fall asleep or nap with the same day, regardless of appropriateness of time or place. occuring at least 3 times per week over the past 3 months, accompanied by at least one of the following: Adult Cataplexy, Childhood Cataplexy, CSF Hypocretin <= 110 pg/mL, 4. PSG/MSLT finding.

ICSD-3 defines narcolepy type 1 as daily periods of irrepressible need to sleep or daytime lapses into sleep occurring for at least 3 months. With the presence of one or both of: Cataplexy and MSLT finding, or CSF hypocretin-1, of either up to 110 pg/mL or <1/3 of mean values obtained in normal subjects.

And narcolepsy type 2 as daily periods of irrepressible need to sleep or daytime lapses into sleep occurring for at least 3 months. And, requires 4 other tests, which are MSLT finding, no Cataplexy, no CSF Hypocretin-1 test or that the test result was > 110 pg/mL, and that the the first two can not be explained away by other causes.

Guess its a snap to never diagnose people with type 2, once you dismiss their reports of Cataplexy.

ICSD-3 also has a subtype of type 2 narcolepsy – due to a medical condition, such as PD, MS, head trauma.

Cataplexy is estimated to be present in ~70% of Narcolepsy cases, but I had heard that the severe form affects less than 10-15%. It is said that Narcolepsy with Cataplexy, “affects about one in every 3,000 Americans. More cases without Cataplexy are likely to exist.”

In the research for this post, I came across “Predictors of Hypocretin (Orexin) Deficiency in Narcolepsy with Cataplexy", where the thresholds are revealed to be from statistical analysis, using R. Where the optimal cutoff for CSF Hypocretin-1, the ROC curve analysis defines a gold standard of approximately 200 pg/mL as the cutoff for the diagnosis of Narcolepsy without Cataplexy vs those with, and is convenient with previously defined cut offs of low (<=110), intermediate (<=200), or normal (>200), where Narcolepsy with Cataplexy are those with 110 pg/ml or less. Intermediate….do we really exist? From what I recall reading (while I was required to lay as still as possible on back follow the spinal tap), those values were again through statistical analysis…putting the mean for Hypocretin levels for normals at ~399 pg/mL, and that 110 pg/mL was two standard deviations below the mean.

Also interesting, was “Survival curve analysis…no patient developed Cataplexy more than 26 years after onset of sleepiness, and that half (48%) with Hypocretin deficiency would eventually develop Cataplexy. When did my onset of sleepiness occur, and how does that correlate to where I had a Cataplexy episode in May 2012 that landed me in the ER (the outcome of that experience was a Dx of Cataplexy.)

And, then, I found “Complex movement disorders at disease onset in childhood narcolepsy with cataplexy", where ” The reported movements are not commonly described in adulthood Cataplexy that is typically characterized by jaw dropping, facial flickering or head dropping […], as well as by twitches of the face and of the limbs occurring during a Cataplectic spell and generally assessed by means of questionnaires” Hmmm…..

See: Narcolepsy Fact Sheet - NIH: NIINDS for more information.

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My second rare disease diagnosis is Spinocerebellar Ataxia. First time I experienced its symptoms severe enough to seek out medical … was September 2002 (very close to the 1 year anniversary, leading to thoughts of conspiracies and such.), It wasn’t until October 15th, 2012 that the primary symptom called Ataxia became a constant in life, I miss the months up to this date where I thought I was finally free of it. Had often wondered if the discontinuation of Ropinirole a couple weeks before had played a part, but got no response from any doctors I’ve seen since. Ropinirole is a dopamine agonist used in the treatment of Parkinson’s disease and restless legs syndrome [Wills-Ekbom Disease]

Though as I look back, my first symptom was probably what prompted my first encounter with a Neurologist in early 2000. I had a tremor, where one of the chief complaints was that when I needed to be precise with my mouse clicks the harder it was to keep pointer steady for that exact location. I was a Software Engineer at the time, where I was tweaking a UI.

This had been a weird visit which seemed to have set the stage for what every doctor since has repeated. After what felt like a thorough work up, the doctor said the strangest thing in revealing his diagnosis to me. He told me that my paternal grandmother (who had passed away in 1995), had been misdiagnosed. She did not have Parkinson’s. What we share is a familial tremor, aka Essential Tremor.

Last summer I found an article explaining Essential Tremor vs Cerebellar Tremor. Familial (Essential) tremor appears during voluntary movement. Most common in the hands, but can manifest elsewhere in the body. They are slowly progressive, but rarely affect the lower half of the body. These tremors cause shaking that appears to be rhythmic, arise repetitively during certain activities or movements in everyday life.

While Intention (Cerebellar) tremor is similar to Essential Tremor, but the difference lies in that little or no tremor is present at the beginning of a movement or action. Instead,as the limb moves t reach its target the tremor appears and/or increases, making the end goal impossible.

There are a variety of medical treatments, such as Inderal (Propranolol), Corgard (Nadolol), Mysoline (Primidone), or Neurontin (Gabapentin) for Essential Tremor. I was on the first in the beginning, and it worked well, but was taken off with explanation but likely the doctor didn’t feel the benefit justified the risk. So, the second became my primary medication for this, doesn’t feel that it had was like the previous, but discontinuation from is quite noticeable. Since 2013, I’ve been on Gabapentin for pain from peripheral neuropathy….had started at 300mg twice a day, and now can take up 900mg three times a day (prescribed as 300mg capsules, so that its 600-900mg….3 times a day. In theory could go to 4, though have found that it interferes with sleep more than not taking my sleep meds on an empty stomach.

After these, there have been use of tranquilizers and botox, along with surgical options.

But,, with Intention tremor, there are no defined medical treatments, as there’s nothing currently for treating the cerebellum and correcting this disorder. So, we’re left to learn to control the problems ourselves. Though some of the above drugs can be helpful in reducing….

While now the means to diagnosis Parkinson’s has become much better, especially to separate conditions that resemble it from PD. Historically one of the ways to diagnose PD, was to treat the person with Ropinirole (requip) or Pramipexole (mirapex), both of which I had been on for RLS/WED. Pramipexole didn’t agree with me (almost immediately), I was eventually able to tolerate Ropinirole (took longer than the planned titration to full dose within 4 weeks.) And, if their symptoms improved, then they had PD.

I had come across references to Parkinsonism in ataxia’s, such as SCA2, SCA3, SCA17, plus some reports for SCA6 and SCA8. SCA3 (MJD) was first genetically confirmed subtype for patients that are levodopa-responsive PD like. I’ve seen clinical trials related to these SCA’s and PD drugs. Unfortunately, I don’t have a positive genetic test identifying what my SCA subtype is.

Later when seeing other Neurologists, when I would reassert my grandmother’s Parkison’s as part of my family history, they would act like it was news to them.

Anyhoo…I got that diagnosis in July 2014.

Last bit, again while researching while writing this post….I came across: “Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy”, something I’m going to stash for later reading.

But first to see about getting out on the weekend for a change….