Hypertension and CADASIL

Disclaimer: I am not a medical doctor nor do I have medical training of any kind. What follows is my understanding of the arteriopathy of CADASIL and the arteriopathy caused by hypertension. I did, however, discuss my understanding of this issue with my CADASIL neurologist before posting.

Note: all photos are irrelevant and are ©pwcimages

High Blood Pressure

Persistent high blood pressure levels are potentially dangerous, leading to an increased likelihood of developing cardiovascular disease that can lead to heart attacks, heart failure, stroke and other unwanted health issues.

I live in Australia and the Heart Foundation here states that any blood pressure (BP) reading from 140/90mmHg upwards is high.

Source: Guideline for the diagnosis and management of hypertension in adults, 2016

This definition of high BP is consistent with that of similar bodies around the world: British Heart Foundation; Heart and Stroke Foundation of Canada; Blood Pressure UK; Southern African Hypertension Society.

In the USA, however, their Heart Foundation definition of hypertension was revised in 2017 (as reported here by Harvard Health) as follows: hypertension Stage 1 (130-139/80-89); and hypertension Stage 2 (140+/90+).

Source: American Heart Association

So When Does High Blood Pressure Become Hypertension?

A one-off high blood pressure reading does not mean that you have hypertension.

Blood pressure levels fluctuate throughout the day and it is possible to have temporary mildly elevated to highly elevated levels, e.g., during a period of high emotional stress; during intense exercise. This is normal.

According to The Heart Foundation of Australia, a diagnosis of hypertension can only be made after “a comprehensive assessment of blood pressure…based on multiple measurements taken on several separate occasions, at least twice, one or more weeks apart, or sooner if hypertension is severe.”  See Guideline for the diagnosis and management of hypertension in adults, 2016, Chapter 4, Evaluation and Diagnosis of Hypertension

 

Why You Really Don’t Want Hypertension

What is it about hypertension that heightens the likelihood of developing the cardiovascular issues I mentioned earlier, and why is it so undesirable in those of us who have CADASIL?

One of the most significant and problematic of the many features of CADASIL is arteriopathy (disease of the arteries). The consequence of that arteriopathy, especially in our small arteries and arterioles, is that, over time, the blood vessel walls progressively become thicker and stiffer. This results in a narrower lumen (the bit through which the blood flows) and much less compliant (elastic) blood vessel walls, meaning they will no longer be able to dilate and contract to accommodate changes in BP levels. And in CADASIL, this happens in the absence of hypertension. So, behind the eight ball already. And long term, ongoing hypertension – in the absence of any other disease factors – leads to exactly the same result, although the mechanisms involved are not the same.

In hypertension, the process of thickening and stiffening of arterial walls is called arteriosclerosis. When it happens in arterioles, it is called arteriolosclerosis (note the slight difference in spelling). And the arterial damage that occurs in hypertension is unable to be reversed (as is also the case in CADASIL).

Whilst hypertension is a common occurrence in elderly people, a combination of risk factors can see it occur much earlier in life. See Risk Factors for High Blood Pressure (Hypertension).

Source: Scielo

Arteriolosclerosis

Arteriosclerosis and arteriolosclerosis are not to be confused with atherosclerosis.

Arteriolosclerosis is a structural change in the affected blood vessel walls of arterioles as a consequence of the sustained pressure of hypertension whereas atherosclerosis is a result of plaque build-up inside the blood vessel.

Arteriolosclerosis

Source: Mechanical Stress and the Arterial Wall

Atherosclerosis

Source: Mayo Clinic

And Arterioles Are Bloody Thin!

The scale at which arteriolosclerosis happens is minute – unimaginably tiny, especially for the terminal arterioles where blood is dispersed into capillaries.

Image Source: Quora

So how tiny is tiny? One µm (micrometer or micron) = 1/millionth of a metre or 1/thousandth of a millimetre. Hard to imagine that something so narrow could have any meaningful structure let alone be able to transport blood. The image above shows arterioles vary in width from 10µm to 30µm (and check out the width of the arteriolar walls!) Compare these widths to: human hair (17 to 181µm); paper thickness (70 to 180µm); wool fibre (10 to 55µm); cling wrap (10 to 12µm); and, spider’s web silk (3 to 8µm). See Micrometre.

What To Do?

Don’t add fuel to the fire. If the pathology of CADASIL means that the walls of our small arteries and arterioles are going to thicken and stiffen anyway – effectively aging them prematurely – do not give them any further reason to do so.

If you have hypertension or are pre-hypertensive, start NOW to make the changes needed to get your blood pressure levels back to as close to optimal as possible. If you are overweight, especially around the tummy (Oo! Oo! Pick me!), drop a few kilos/pounds; get rid of the salt (read those food labels, and drastically reduce how much you add to food); if you smoke, STOP… RIGHT NOW (well, ASAP). Smoking contributes to arterial damage (it’s not just bad for your lungs). Read here for other cardiovascular risks that arise from smoking and a list of suggestions to help you quit; if you aren’t already, get physically active – yes, my body is in pain all the time too (start gently and, as you feel able, work up to moderate intensity – see Physical Activity Guidelines); talk to your doctor about starting, or modifying, blood pressure medication – there are plenty of options available; reduce exposure to, and manage, stress – plenty of options here as well; get enough sleep – easy to say, I know…I don’t get enough myself, in terms of quantity or quality; cut back on the alcohol –  but you don’t need to get rid of it entirely. See High Blood Pressure Treatment.

None of this is easy. We are creatures of habit and changing the habits of a lifetime can be bloody hard! You’ll procrastinate initially; you’ll make false starts; you’ll doubt yourself; you’ll feel physically and emotionally horrible at times; you’ll get frustrated and angry.

Persist. Know that others will accept what you are trying to do and why. Know that others have been down the same path and understand what it feels like.

Be easy on yourself. Forgive yourself. Have faith in yourself.

It’s worth it.

’til next time,

thecadasilblogbloke

 

 

So, How Rare Is CADASIL?

What does “rare” mean anyway?

We all have a notion of what the word “rare” means.  “Very few”, “hardly any”, “almost none” and similar phrases come to mind.

To place it in some kind of context, I find it helpful to think about the status of certain species of wildlife – are they abundant? Common? Uncommon? Threatened? Critical? Rare? Or, tragically, extinct?

And yet, as it turns out, when it comes to diseases, asking what is rare happens to be a reasonable question.

So, what is a rare disease?

Well, there is no internationally accepted or agreed definition of the term “rare disease”.  Yes, you read that correctly.

Even the terminology itself isn’t a universally agreed one.

In 2015, the International Society for Pharmacoeconomics and Outcomes Research, aka  ISPOR, released a report from their Rare Disease Special Interest Group that canvassed this very issue. Their global search found 296 definitions spread across 1109 organisations, with the terms “rare disease(s)” and “orphan drugs” being the most commonly used. In terms of numbers, the average prevalence or penetration rate for rare diseases as a total was 40 cases per 100 000 of the population, with the defined range in individual jurisdictions varying quite widely from 5 to 76 per 100 000 of the population. You can read more here: Rare Disease Terminology and Definitions—A Systematic Global Review: Report of the ISPOR Rare Disease Special Interest Group

And it even gets a little more complicated than that, as some countries determine what a rare disease is based on a prevalence rate (<1 in 2000 people in Australia and the European Union) and others as an absolute number (<200 000 people in the USA).

Irrelevant Photo 1: a rare example of an Australian acacia flower  (there is usually full coverage, not a gap as seen here). ©pwcimages

Okay, but how rare is CADASIL?

When my mother was diagnosed here in Australia with CADASIL in late 1998 (and the disease name ‘CADASIL’ only came into being in 1996), our family was told that the disease is rare and affected about 400 families around the world.  Using any of the prevalence rates mentioned above, that made CADASIL more than rare – that put it in the category of ultra-rare or super-rare! At the time the United Nations estimated the world population to be 5.9 billion, so 400 families represented a mere speck inside a drop in the ocean.

In 2006, the 400 families figure was still being quoted and even again as recently as 2013 (see second paragraph under “Discussion”).

Estimations of Prevalence

Attempts to estimate prevalence in specific regions, including the west of Scotland and the north-east of England, have been made over the years but getting a better global estimate has been elusive.

The rare diseases online portal Orphanet states that the prevalence rate of CADASIL in Europe is somewhere between 1/50 000 to 1/25 000 people (information checked online Friday 3 August 2018).

Irrelevant Photo 2: the prevalence of CADASIL is thought to be 2/100 000 to 5/100 000. ©pwcimages

What’s The Latest?

According to a paper published on 24 February 2017,  Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects, the latest estimate of the prevalence of CADASIL worldwide as at 2016 was thought to be in the range of 2 to 5 in 100 000 of the population (which roughly accords with the Orphanet figure).

The estimate is based on only four different studies, including the two mentioned above in Scotland and England (all of the relevant studies are cited in the 2017 paper), evidence that there have, indeed, been very few attempts to establish the prevalence of CADASIL over the years.

Note also that the 2017 paper states that there are now known to be thousands of families, amongst a diverse range of ethnicities and countries, affected by CADASIL.

Whatever way you look at it, CADASIL is rare but it is certain that it remains underdiagnosed and, therefore, the prevalence rate may be higher than it is currently thought to be.

’til next time,

thecadasilblogbloke

New CADASIL Facebook Group – Australia, New Zealand, Oceania

CADASIL Oz/NZ

Today sees the launch of a new CADASIL Facebook group for people living in Australia, New Zealand and the wider Oceania region.

To say the least, CADASIL is a challenging disease to live with, for anybody and no matter where you live. In our part of the world, it is exacerbated by the “tyranny of distance”. I hope this FB group helps to shorten those distances.

https://www.facebook.com/groups/258659084702051/

’til next time,

thecadasilblogbloke

“Shit, I DO Have CADASIL” to “So, okay… I have CADASIL”.

“Shit, I DO Have CADASIL”

As I’ve said in an earlier post, finding out I had CADASIL was no surprise. My Mum had been diagnosed several years earlier; her mother almost certainly had it, having had many strokes in her lifetime, with obvious deterioration in her physical and cognitive health over that time; and I had been having migraine with aura for too long already.

The first few months after my diagnosis, nevertheless, saw me feeling despondent, more depressed than usual, lacking enthusiasm. I felt vulnerable and void of hope, apathetic, listless. The migraines kept on coming.

When I had a meeting to tell my manager about my confirmed diagnosis, he asked “is it genital”? I laughed. Hard. Close to the point of crying. He quickly corrected himself – “I meant congenital”.

Work was as busy as it can ever get at the Australian Bureau of Statistics. We were only a few weeks away from conducting the 2006 Census of Population and Housing. It’s a mammoth undertaking – the ABS had employed over 30 000 temporary workers to deliver, follow up and collect the Census forms. In the days immediately before Census night, calls to our National Information and Referral Service had escalated tenfold, maybe more.

Irrelevant Photo No. 1: ©pwcimages

My stress levels were high.

I wasn’t as attentive, or as present, as usual. My mind was elsewhere, I was completely self absorbed. I was struggling to “keep it all together”. I kept volunteering on a weekly basis at my daughter’s school, helping with learning to read and doing maths. Most of the time I didn’t feel like going but was always glad I did. The migraines persisted.

I had been obsessing about CADASIL since not long after Mum was diagnosed and I had become familiar with the symptoms that come with it. My migraines with aura were especially troubling, both in terms of their horrid effect on me and the omen they represented in terms of my possibly  having that shitful disease.  My anxiety shot skywards and I wondered every day for seven years if I might have it before deciding – finally – to be tested.

To be told for certain I have CADASIL felt like being told to “get my affairs in order”, or something like it anyway. I kept obsessing for some time after being diagnosed.

Irrelevant Photo No. 2: ©pwcimages

One day, I realised I hadn’t thought about CADASIL at all during the previous day. It sort of coincided with (I think) a subconscious realisation that my condition hadn’t worsened. I became aware that CADASIL existed on a spectrum, in terms of symptoms, clinical effects, quality of life, severity, life expectancy and more. I’m towards the benign end.

My days of not thinking about CADASIL extended into weeks and, sometimes, months.  Over the years, my diagnosis moved from being an anvil slung around my neck to being a source of reassurance. That sounds odd, I know. But I had come to appreciate the certainty it provided. My symptoms were explained – I no longer had to search for an answer. And once it was obvious I have a benign form of the disease, I accepted that it is part of me.  I don’t like that I have it but I accept that I have it. (Although, I don’t think I would be so accepting if I had a more aggressive form of it.)

Eventually, I woke up one day and thought to myself…

“So, okay… I Have CADASIL”

’til next time,

thecadasilblogbloke

CADASIL Guides for the Layperson

Just wanted to throw together a couple of general information guides about CADASIL that are written (mostly) in Plain English.

Cambridge CADASIL Clinic

CADASIL Brochure jointly produced by the Neurogenetic Outpatient Department of the Grosshadern Clinics and the Memory & Aging Program at Butler Hospital 

And one slightly more technical paper that is also extremely useful, especially to give to your doctors…

but give them the other ones as well!

CADASIL – An Update on Clinical, Diagnostic and Management Aspects

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0778-8

(All images are irrelevant to the post and are ©pwcimages.)

’til next time,

thecadasilblogbloke

 

“You Have CADASIL”

Mid-morning of Friday, 16 June 2006, I was sitting with my wife in the waiting room of the Royal Ambulatory Centre at John Hunter Hospital (JHH) in Newcastle, New South Wales. It is a large waiting room, with seemingly endless consulting rooms running off to the east and west. Patients and their partners, families, friends sat in their allotted areas, some quietly, some speaking in hushed tones, some with kids being kids. A small line of outpatients waited to be processed at the reception desk. Medical specialists drifted in as the time came to see their first outpatient of the day.

Glass formed almost the entire wall on the northern side of the room, overlooking the suburb of Lambton and then taking in sweeping views that spread all the way to Port Stephens, a stunning coastal region and holiday destination about an hour’s drive to the north-east. Cumulus clouds were scattered over the wide sky, drifting gently to the east.

John Hunter Hospital ©theherald.com.au

“Patrick?”

My wife and I looked toward where the voice had come from.

Thirty seconds later we were sitting in a spacious but otherwise unremarkable consulting room. My stroke neurologist – Professor Christopher Levi, Co-Director of the Acute Stroke Unit at JHH and Director of Clinical Research and Translation for Hunter New England Health – was sitting at a corner desk, near the door, on which a computer monitor was displaying MRI brain images – my brain, I suspected.

Professor Chris Levi ©newcastle.edu.au

If I was going to get unwelcome news about my health, I’d want it to come from this bloke – he is engaging, respectful, personable, has a great “bedside” manner and knows his stuff, right on top of his game.

He summarised how we had jointly got to this point. My Mum’s diagnosis seven years earlier, following an otherwise inexplicable stroke; my sister’s mysterious case of catatonia following the birth of her fifth child; the severe migraines that came on after the births of all her children; the family consultation we had had with Chris not long after that.

During that consultation, my decision to get tested was instant – no hesitation; no need to think about what it might mean; no need to see a genetic counsellor (I worked then at an Obstetrics and Gynaecology lab who had genetic counsellors to report increased risks of birth defects to pregnant patients).

For several years, I had been living as if I did have CADASIL anyway. I had obsessed about it – thought about it every day. I was getting no peace of mind. The stress was unrelenting. My concentration was waning, my moods were vascillating, I was more irritable and depressed. And, if it was at all possible, even more self-obsessed and selfish.

Migraine with aura had been plaguing me on a regular basis and, as best as I could tell, I had no triggers that set them off. Beyond that, I had a gut feel that a 50/50 chance of having inherited this disease hadn’t worked in my favour – my other sister and my brother didn’t get migraines, and they were more even-tempered than me, my mother and the elder of my two sisters. The last point is irrelevant to CADASIL but I saw it as an omen.

The exact words elude me after all this time. “Patrick, as we suspected, you do have CADASIL.” “Well, Patrick, the blood test does confirm that you have CADASIL.” “As you know, Patrick, your MRI was strongly suggestive of you having CADASIL and…”

Even though the news was completely expected, there were tears. I knew this result was coming but, truly, expecting such news, and receiving confirmation of it, are worlds apart. My wife grasped my hand and shared my tears.

What occurred throughout the remainder of the consultation is long gone, long forgotten. My wife and I returned to our car and set out on our return trip to Sydney, where our six year-old daughter was struggling to make friends at school and my workplace at the Australian Bureau of Statistics was in final preparations for the largest peace time operation in Australia – conducting the national Census of Population and Housing.

The world didn’t look any different than it had when we had driven up that same freeway a few hours earlier.

’til next time,

thecadasilblogbloke

Photo: utterly irrelevant. North Curl Curl headland, Sydney, NSW, Australia. ©pwcimages

That tingly tingling feeling

It’s just a headache…right?

As a child aged 10 or 11, I recall having a severe headache that kept me in bed for a couple of days. It may have been a migraine, it may not. Aged 26, I had another severe headache. This time I knew it was a migraine.

I had been home for a quarter of an hour or so, after a 30 minute walk from work. I started getting a very mild tingling at the ends of my right fingertips and it began to move slowly up through all of my fingers, then the rest of my hand and up to my wrist. By the time the tingling had reached my wrist, the lower half of my fingers had recovered their normal feeling.

Within minutes, this wave-like pattern of tingling,  accompanied by moderate muscle tightness, had rolled up my entire right arm in a slow pattern of constriction and then release. It was like a narrow band of a weird sensation scrolling up my arm, no more than a centimetre or so in width. Tighten, release. Tighten, release. And all the while crawling with determination towards my shoulder.

On reaching my head, it worked it’s way from the top of my scalp down.  When the tingling reached my nose, it felt liked I wanted to sneeze but couldn’t. Aah, aah…aah, aah…

The right side of my lips and tongue felt huge, swollen as if a dentist had needled anaesthetic near my back molar. I was sure that if I looked in the mirror at that point, I would look grotesque.

Instead, I rang my wife at her workplace. I couldn’t speak properly; pronouncing words incorrectly and struggling to find the appropriate words.

The movement through my neck felt strange. Was this what it felt like to be “lightly” strangled, by a one-handed strangler?

The tingling continued with an unerring rhythm – crawl, tighten, release; crawl, tighten, release. Feeling it progress through my chest and stomach, affecting only my right side…was…unnatural.

By the time the tingling could progress no further, and it exited my big toe, 30 minutes had gone by. Not long after, the pain hit. And it was unbearable.

So began my decades-long, intimate relationship with migraine with aura. I soon came to learn that what I had experienced was a one-sided parasthesia and they went on to become a familiar part of my migraine routine. I even had a few occasions where I experienced double parasthesia within a 24 hour period. And parasthesia with no following pain. And “incomplete” parasthesia that aborted half way up my arm, or went no further than my fingers. Almost always, they afflicted only the right of my body.

Over the years, my migraines have lasted from four or five days up to two weeks, from the prodrome to the postdrome. They have varied in pain from 0/10 (the silent migraines) to 100/10 – yes, that’s not a typo. They have been throbbing, searing, booming, pounding, sharply and piercingly focussed, broadly spread and dense, like an impenetrable fog.

Our relationship continues…but we don’t see each other as much as we used to…

’til next time,

thecadasilblogbloke

My brain trying to focus during a migraine. ©pwcimages

That Fateful Day

The Drive to Newcastle

As I drove from Sydney up the F3 freeway in late spring on that November day in 1998, my almost five-month pregnant wife sat quietly next to me. It wasn’t entirely quiet though – we were listening to a pop radio station and traffic regularly passed us by in its rush to get who knows where.

I had driven up and down this route many, many times. Today the weather was fine, the amount of traffic was moderate and the driving was not stressful, unlike Friday nights and late Sunday afternoons when, respectively, people flee Sydney at the end of the work week and grudgingly return as late as possible on the Sunday.

It was a straightforward, if somewhat boring drive that day.

I wasn’t sure what to expect when we arrived at John Hunter Hospital in Newcastle, a couple of hours after leaving our home in Cammeray, on the lower north shore of Sydney. I’d received a phone call (was it from my Dad? was it from one of my sisters?) to tell me that Mum had had a stroke.

Not long after being admitted to her small local hospital in Scone, she had been transferred to the John Hunter for more specialised care in a stroke unit.

The Hospital

After an uneventful drive, I parked the car in the back parking lot of the hospital. I felt my body tense up a little. Anxiety? Anticipation? A consequence of being stuck in the same position for a bit over two hours?

You see, Mum and I had a fractious relationship. We were both volatile, quick to anger with short tempers, hopeless at expressing and showing our love for each other and, on social issues, we were miles apart. My wife being pregnant out of wedlock was a source of anxiety for her.

As we walked to the back entrance of the hospital, we passed two or three very pregnant woman standing nearby, slightly apart from each other, smoking.  Mum had been a smoker for a long time, as had Dad until the result of an on-the-spot cholesterol test at a school fete a few years before led to him quitting alcohol and smoking, cold turkey. But Mum had never been a heavy smoker; just a few times a week and never more than one or two at a time. As for drinking, barely any.

We entered Mum’s room and found her propped up in bed, surrounded by other members of the family. She was very red in the face, seemed a little confused and disorientated. She could speak and, from memory, had no major deficits from the stroke. All things considered, she didn’t seem too bad – not great but not too bad.

Unexpected and Unwelcome News

Her staff neurologist was unable to explain why Mum had had a stroke. A few days later, he mentioned she might have CADASIL. She might have what?

It took a long time to remember what that acronym stands for, let alone what it means. I soon learnt that it is not a good disease to have, that it is rare , and that me and my three siblings had a 50 per cent chance of inheriting it when we were conceived. It also seemed to mean that, if we also had it, we would have an early death.

Oh…and there is no treatment and no cure.

’til next time,

thecadasilblogbloke

CADASIL? What the…?

CADASIL is an acronym, short for a bit of a shitty disease called Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. But if you found my blog, I’m going to guess that you already know that. Unless, of course, you were looking for something else entirely and somehow your favourite search engine threw this in your face.

Okay, let’s assume for a second that that’s what happened to you. Let’s break it down. “Hey! Where are you going? Stick with me here…it gets mildly interesting.”

• Cerebral: related to the brain; affecting the brain.
• Autosomal Dominant: CADASIL is caused by a defective gene. You only need one parent with such a gene to pass it on to you at the time of your conception. About nine months later, you will be born with CADASIL.
• Arteriopathy: a disease of the arteries.
• Subcortical: a region of the brain that is below the cortex. The cortex is the outer layer of the brain…you know, that pinky-grey stuff that is full of folds and curves. Hence, the sub-cortex is the deeper part of the brain, sometimes referred to as the lizard brain, reptilian brain, or mammalian brain.
• Infarct: a small region of dead tissue caused by a blockage of blood supply in that region.
• Leukoencephalopathy: disease that affects the white matter within the brain. White matter is found in the subcortical region of the brain (the deeper part of the brain I mentioned above) and it is comprised of nerve fibres (axons), most of which  are bundled together and covered in protective sheaths called myelin. Apart from protection, the purpose of myelin is to process and provide a pathway for nerve signals to move throughout the brain. The colour of myelin is…white…well, whitish.

CADASIL is a progressive neuro-degenerative disease, once thought to be rare but, I suspect, soon to be upgraded to “uncommon”. Although one is born with it, symptoms do not appear until later in life. Onset of symptoms is variable, as is the number of symptoms that affect each individual within the CADASIL population and the age at which they become apparent. Severity of the disease is also highly variable, even between family members.

Although not shared by all people who have CADASIL, the main symptoms can include: migraine (usually with aura); trans-ischaemic attacks (TIAs); mild ischaemic strokes (usually lacunar in nature); mood disorders (depression and/or anxiety). Repetitive strokes eventually lead to dementia. Some people display a range of other symptoms as well, more of which in future blog entries.

’til next time,

thecadasilblogbloke