Tag Archive | progressive supranuclear palsy

The Layperson’s Guide to Neural Disorders That Often Lead to Neurodegeneration and Dementia

Normal brain cellMost dementias – Lewy Body dementia, vascular dementia, early-onset dementias, alcohol-related dementia, and Alzheimer’s Disease among them – appear seemingly suddenly as primary and distinct neurodegenerative processes without definitive causes (except in the case of genetic inheritance, which primarily occurs in rare dementias like Corticobasal Degeneration, Progressive Supranuclear Palsy, and Fatal Familial Insomnia and some of the early-onset dementias).

However, there are a group of neural disorders, which are caused by the same genetic mutation that affects lipid storage in the body, that often have dementia as a secondary symptom as the diseases progress.  

Structure of cell membraneThese neural disorders (all these have sphingolipid metabolism dysfunction in common) – which include Niemann-Pick disease, Tay Sachs disease, and Gaucher disease – are characterized by by increased levels of a particular type of sphingolipid.

There is no cure for these neural disorders and they are all fatal (in many cases, during childhood).

Anatomy of a sphingolipidSpingolipids are the biological product of a chemical process that creates a protective layer on nerve cell membranes and ensures proper – and protective – cell signaling and are critical to optimal brain function.

The genesis of sphingolipids are long-chain – also known as sphingoid – bases that normally have a length of 18 carbons, although they can also have lengths of 16 or 20 carbons. The length of long-chain bases is determined by serine palmitoyltransferase (STP), a multiprotein enzyme.

Chemistry of sphingolipidIn neural disorders like Niemann-Pick disease, Tay Sachs disease, and Gaucher disease, a mutation (known as Stellar) in one of the proteins that makes up STP creates an abnormally high number of 20 carbon long-chain bases, which dramatically interferes with sphingolipid metabolism.

This causes neurodegeneration to occur. In all these neural disorders, much of the neurodegeneration begins soon after birth.

In Tay Sachs disease, neurodegeneration of the brain and spinal cord begins at about six months of age. The average lifespan is four years.

Gaucher disease has three subtypes.

In Type 1 Gaucher disease, symptoms, which include anemia, bone deterioration, and liver and spleen impairment, are non-neurological and do not materialize until middle age. The average life expectancy for Type 1 is 68 years.

Type 2 and Type 3 Gaucher disease are both neuropathic forms of the disease.  Neurodegenerative symptoms include abnormal eye movements, seizures, and systemic brain damage.

In Type 2 Gaucher disease, the onset of symptoms is within three to six months of age. Deterioration is rapid; the average life expectancy is about two years of age.

 Type 3 Gaucher disease is a slower onset and involving version of Type 2. The average onset of neurological involvement is late childhood into adolescence. Life expectancy ranges from the mid-twenties to, in extremely rare cases, the early forties.

Niemann-Pick disease has four types: Type A, Type B, Type C1 and Type C2.

Niemann-Pick disease Type A occurs in infants. Symptoms include enlargement of the liver and spleen (around three months of age) and a failure to thrive during the first year of life. At one year, widespread damage to the lungs occurs, and there is a progressive loss of neurological and motor function.

A cherry red spot on the macula is a common denominator in Tay Sachs Disease and Niemann Pick disease Type 1Along with Tay Sachs disease, Niemann-Pick disease Type A also has a common eye deformity consistent with neurometabolic disease, known as a cherry spot, that occurs within the macula and is often what initially identifies the two neural disorders.

While most children born with Niemann-Pick disease Type A die in infancy, a few may live as long as four years.

Niemann-Pick disease Type B includes most of the same symptoms as Type A (motor skills are not usually affected), but the onset of symptoms is during adolescence. Most people with Niemann-Pick disease Type B survive into adulthood, but mortality rates climb dramatically between twenty and thirty years of age.

Niemann-Pick disease Type C (C1 and C2 are caused by different gene mutations, but the symptoms are the same) is characterized by severe liver disease, severe pulmonary infections, progressive neurodegeneration, and increasing difficulty with speech and swallowing that deteriorates completely over time.

The onset of Niemann-Pick disease Type C can be at any age, but it is most commonly seen by the age of five. The life expectancy with this type is under twenty years of age when symptoms appear in childhood. When symptoms appear later, the life expectancy is ten to twenty years after symptoms begin.

 

 

The Rare Dementias: Corticobasal Degeneration (CBD)

Corticobasal degeneration (CBD) – also known as corticobasal ganglionic degeneration (CBGD) – is a rare (occurs in less than 1% of the population) and progressive form of dementia.

The onset of symptoms typically occurs after the age of 60 and the average duration of the disease from onset of symptoms to death is six years.

Although the underlying cause of CBD is unknown, what is known is that CBD is the result of extensive and severe damage in multiple areas of the brain.

Research into this form of dementia is relatively new (it was discovered in 1968), but the most current research has found that there are similar, but not identical, changes in the brain protein tau to the changes observed in progressive supranuclear palsy and Pick’s Disease.

lobes of brainThese areas of the brain where damage is extensive include the cortex (especially in the frontal lobe and parietal lobes) and the deep-brain basal ganglia region of the brain, with the hallmark feature in that area being significant neuron degeneration and the loss of pigment in dopaminergic neurons (signifying a decrease in dopamine production) in the substantia nigra, which controls movement. 

Dopamine is a chemical produced by the brain (a neurotransmitter) that plays a leading role in movement, memory, pleasure,  cognition, behavior, attention, sleep, and mood.

basal ganglia substantia nigra dopamine movement corticobasal degeneration CBD dementiaWhen dopamine production decreases in the substantia nigra, movement is severely affected.

Often this is the first visible symptom of CBD. It presents as stiff movement, shaky movement, jerky movement, slow movement, and increased lack of balance, increased lack of coordination, and clumsiness. Generally, movement problems affect one side of the body almost exclusively, but as CBD progresses, both sides of the body are affected.

Since these movement disorders can mimic both Parkinson’s Disease and the effects of a deep-brain stroke –  one of the classic movement disorders associated with these is ideomotor apraxia (a common example is the inability to initiate walking where the foot seems to be stuck to the floor and can’t be lifted spontaneously to take a step forward) –  those must be ruled out as the causes of the movement disorders.

Other early symptoms of CBD can include difficulty controlling the mouth muscles, cognition problems, and behavioral problems. Language and speech difficulties – dysphasia (an impaired ability to understand or use the spoken word) and dysarithia (an impaired ability to clearly articulate the spoken word) – are also early CBD symptoms.

(In my latest book, You Oughta Know: Recognizing, Acknowledging, and Responding to the Steps in the Journey Through Dementias and Alzheimer’s Disease, I devote a whole chapter to a comprehensive and in-depth discussion of the communication problems, including the different types of dysphasia, that occur with dementias and Alzheimer’s Disease, and ways to work with our loved ones to keep the lines of communication open for as long as possible.)

It is not unusual for CBD to be initially diagnosed, if the first symptoms are cognitive impairment and/or behavioral issues, as Alzheimer’s Disease or frontotemporal dementia. Similarly, if movement disorders are the first symptoms, CBD is often initially diagnosed as Parkinson’s Disease.

However, a clear diagnosis of CBD is usually made when both movement disorders and cognitive impairment and/or behavior problems appear simultaneously.

There is no known treatment for CBD. Unlike Parkinson’s Disease where dopamine-enhancing or dopamine-mimicking medications prove to be effective for some of the duration of the disease, these drugs have proven to be ineffective for treating CBD (this is likely because of the very different pathologies in the development and progression of the two diseases).

In the early stages of CBD, speech therapy and physical therapy may help with communication and stiffness and movement. However, as the disease progresses, these will become less effective and, in the end stage, they will be completely ineffective.

As CBD progresses, other symptoms appear and worsen, including:

  • Rigidity
  • Tremors
  • Involuntary muscle contractions
  • Involuntary eyelid spasms
  • Loss of sensory functions
  • “Alien hand/limb” syndrome (hand or limb movement that the person isn’t aware of nor has control over)

Because of the increased rigidity and lack of muscle coordination and use as CBD progresses, usually within five years of onset, sufferers will be unable to swallow and will be completely immobile. Even before this, though, one of the potentially-fatal risks associated with CDB is aspiration of food into the lungs because of impaired swallowing and the high likelihood of pneumonia as a result.

While a feeding tube may be considered as an alternative when CBD has progressed to the point where swallowing is significantly affected, it is, in my opinion, inhumane because it only prolongs the suffering from a disease that is ultimately fatal.

This is a quality-of-life choice. I can’t imagine for myself a life prolonged where I am completely immobile and completely dependent on everyone else for everything and I can do nothing for myself.

A feeding tube would be my worst nightmare. And for me, it would be the most cruel thing those in charge of making medical decisions for me could do to me.

Fortunately, I already have all my documents in place to make sure this can’t and won’t happen to me when and if the time comes that the choice needs to be made, because I’ve already made the choices. 

So, as an aside, I would strongly urge everyone who reads this to get your wishes formalized and signed and communicated so that you have control over the end game of your life in this area.

Not only is the wise and prudent thing to do, but it eliminates the agony of wondering what to do so often seen in families where the person affected never talked about what he or she wanted and never took the time to answer these questions when he or she could.

 

 

 

The Rare Dementias: Progressive Supranuclear Palsy

This post will begin a continuing series of posts that looks at rare types of dementia. Today’s post will look at the dementia of Progressive Supranuclear Palsy.

Since this blog is primarily original and unique content that provides real education and real resources and understandable information that you can actually use (you’ve no doubt noticed that, unlike many of the blogs that purport to “talk” about Alzheimer’s Disease and dementias, Going Gentle Into That Good Night does not flood your email each day with many, many blog posts that are either old news, political advocacy, or simply forwarded items from some other source, but instead does the medical and scientific research and translates that into usable and practical information for you), I  will provide a clarification that I often do here.

Too many times, I hear the term “Alzheimer’s Disease” used to characterize any and all neurological damage, decline, and death.

That characterization is wrong. 

Dementias refer to the full category of unique terminal neurological diseases that result in irreparable damage and destruction in the brain that lead to cognitive impairment, cognitive decline, and are always ultimately fatal. 

Alzheimer’s Disease is one type of dementia. However, not everyone who suffers from dementia has Alzheimer’s Disease. And sometimes people who suffer with dementia have more than one type of dementia happening concurrently (these are called mixed dementia diagnoses). 

I’ve had people who’ve never dealt directly with dementias kind of wave me off with a “whatever!” reaction when I correct them on this. And I understand that if someone hasn’t had to deal with these dementias day in and day out, they really don’t know and it doesn’t seem like a big deal.

However, for those of us who are dealing with it day and day out – or who may be in the future dealing with it day in and day out – it’s a really big deal.

Why? Precision in defining and understanding the types of dementia is absolutely critical both in caring for our loved ones, but also in effectively addressing the symptoms and behaviors associated with each dementia.

I’ll explain this in an analogy.

Let’s say you or I got diagnosed today with hypertension (high blood pressure). The normal pharmacological treatment is a medication to lower the blood pressure and possibly statins or beta channel blockers to supplement the efficacy of the main medication.

Your physician gives you the diagnosis of hypertension followed by the statement “it’s about the same thing as cancer,” and then sends you to the local hospital for radiation treatment, to be followed by chemotherapy.

Absurd, right? And yet while this may be obviously absurd to nearly everybody, a lot of those people don’t make the connection to the same absurdity of classifying all dementias as a single type of dementia.

But this underscores why it’s just as important to know about the different types of dementias and how to address and respond to the unique areas of the brain they affect as it is to know that you don’t treat hypertension with radiation and chemotherapy.

I have full-information posts on this blog about some of the more common types of dementias and symptoms/behavioral treatments:

And that’s why I want to cover some of the rarer types of dementia now. There’s no substitute for education.

We’re all, if we haven’t already been, going to be personally effected by these diseases at some point in our lives.

We can either be knowledgeable or we can spend time that we should be focusing on our loved ones playing catch-up because we didn’t take advantage of this opportunity to learn about these neurological diseases now.

Progressive supranuclear palsy (also known as Steele-Richardson-Olszewsky syndrome) is a rare neurological disease that, over time, irreversibly damages neurological cells, primarily in the brain stem, causing a severe degradation of gait, balance, complex eye movements, and thinking.

Because gait and balance are primary symptoms of progressive supranuclear palsy, this neurological disease is often misdiagnosed as Parkinson’s Disease. However, progressive supranuclear palsy has unique characteristics that differentiate it from Parkinson’s Disease.

brain-stem-progressive-supranuclear-palsy

The brain stem handles many of the critical functions of the body, including eye and mouth movement, balance, breathing, consciousness, swallowing, sensitivity to external conditions (heat, cold, pain, pleasure, etc.), and hunger. 

The earliest symptoms to emerge with progressive supranuclear palsy are with gait and balance, leading to unexplained falls. Frequently the falls are described by those experiencing them as sudden attacks of dizziness.

Other early symptoms include marked personality changes, including apathy, increased irritability, increased aggravation, inexplicable angry outbursts, and increased forgetfulness.

As progressive supranuclear palsy advances, the characteristics that distinguish it from Parkinson’s Disease begin to appear in vision problems.

The first two vision problems to materialize are blurry vision and difficulty controlling eye movement. It is usually when these symptoms appear that progressive supranuclear palsy can be accurately diagnosed.

People suffering with this neurological disease will, by this point in the disease process, experience severe difficulty voluntarily shifting their eyes to a downward gaze and in controlling their eyelid movements. 

This lack of control over eye movement can result in exaggerated or infrequent blinking (infrequent blinking can cause serious damage to the eyes including severe dryness and ulcers on the surface of the eye) and not being able to close the eyelids or to open the eyelids.

As these symptoms appear, other symptoms also emerge. These include increasingly slurred speech and frequent difficulty in swallowing solid food and liquids (dysphagia).

There are currently no definitive treatments for progressive supranuclear palsy.

There is some research that has shown botulinum injections (Botox) can be an effective treatment for the involuntary eye movements associated with this neurological disease. However, Botox carries its own risks and the benefits of using this as a potential therapy must be weighed against those.

The normal treatment for gait and balance problems – medication and physical therapy – have, to-date, proven ineffective. Therefore, sufferers of progressive supranuclear palsy must use weighted walkers and must have human assistance when walking. Eventually, the problems become severe enough and safety becomes a high enough concern that people suffering from progressive supranuclear palsy are confined to wheelchairs.

The symptom of dysphagia is the most dangerous and the most likely to have a fatal outcome. This is because of choking and the high likelihood of aspirating food back into the lungs. Aspiration often leads to pneumonia, and in this class of neurological diseases, pneumonia is very often fatal.

The only way to address this aspect of progressive supranuclear palsy is to change to the texture of the food. The National Dysphagia Diet Levels is the standard progressive list used to determine food consistency levels as dysphagia worsens.

However, at some point, all ability to swallow anything will be lost, so even if pneumonia is avoided or successfully treated, the time will come when people suffering from progressive supranuclear palsy will not be able to take any kind of nourishment or hydration. This, then, would be the other eventual cause of death from this neurological disease.