Monthly Archives: December 2017

March 20, 2014

LEWY BODY DEMENTIA

Alexander explained that he went 20 years before getting an accurate diagnosis of LBD.  One symptom was significant fatigue, misdiagnosed as Chronic Fatigue Syndrome.  Another was losing his sense of smell.  10-15 years into these strange symptoms was REM Sleep Behavior Disorder, which has since been closely linked to LBD, but at the time was not.  Now, these things are considered early warning signs of PD, but at the time doctors didn’t suspect because he still doesn’t have any significant motor or gait symptoms.  He was misdiagnosed with Alzheimer’s even in the presence of hallucination and perceptual symptoms.  Only when he did his own research was he convinced he did not have Alzheimer’s, but LBD.  He discovered a neurologist as a forerunner in the field of LBD and flew to him to confirm that diagnosis.  At the time he was surprised at the ignorance of neurologists about LBD.  He has since found they are most curious to learn about it.

Alexander is working on a humorous monologue called “Braking for Alligators.”  He hallucinated, and braked for, an alligator in Massachusetts.  He believes humor is very powerful in taking some of the weight off the experience of having such a serious diagnosis with disturbing symptoms, like hallucinations.  Humor is something he can still offer others.

Dr. David Standaert is not surprised that 20 years ago doctors didn’t use the term LBD.  The name was coined in the late 1980s and even in the early 90s they knew very little about it.  It would have been called atypical Alzheimer’s or atypical dementia until the late 90s when they were able to find Lewy bodies in the brain and understand their significance in this neurodenegerative disorder.

Lewy bodies are an abnormal structure found in the dopaminergic neurons in Parkinson’s disease.  In the late 90s, researchers discovered the protein alpha synuclein, which is a major component of Lewy bodies.  That opened the door in looking across the brain.  Researchers discovered that those people who had dementia and other associated symptoms Alexander described (including hallucinations) had these Lewy bodies all over the brain.  These Lewy bodies are hard to see unless you stain for alpha synuclein, then they are obvious.  LBD doesn’t typically have forgetfulness, like Alzheimer’s.

Dr. Susan Bressman says the abnormally mis-folded, or clumping proteins are a common phenomenon of other neurodegenerative disorders (MSA, PSP), as well.

Dr. Standaert believes that they will ultimately find that Parkinson’s Disease (PD) and LBD are the same condition (the basic disease process is the same in these two disorders) manifesting in different ways.  Dr. Bressman agrees.

Alexander has participated in research at the Mayo Clinic.  The DAT scan shows the dopamine deficit even though he doesn’t have typical movement symptoms.  Dr. Bressman suggests the area of the brain affected determines what symptoms manifest so Alexander has RBD, loss of smell, hallucinations (pre-motor features).  Alexander does take some Neupro, which, at a higher dose, worsened his hallucinations.  He still takes a low dose.

MULTIPLE SYSTEM ATROPHY

Dr. Bressman says MSA can be clinically difficult to distinguish from PD.  One form has a cerebellar effect with more unsteadiness and uncoordination symptoms.  There is also a Parkinson’s form with really does mimic Parkinson’s.  What helps distinguish it from PD are problems with autonomic issues like bladder and blood pressure control very early in the progression of the disease.  It can take years to feel confident which diagnosis is correct.  There is a lot of overlap in the pathology, but in MSA, instead of the neurons, alpha synuclein pathology is in the glia supporting cell.  The glia cells in the brain have inclusions.  Treatment overlaps as well.

Dr. Standaert agrees with Dr. Bressman.  There’s no test to distinguish between MSA and PD during life.  People are working on one.  As a neurologist follows a patient over years symptoms become more distinct, like when motor symptoms do not respond well to PD medications, and when there are a lot of early autonomic symptoms.  In MSA there are very few cognitive problems.  Under a microscope, you would not mistake MSA for PD.  It is still alpha synuclein, but it is in the glia in MSA rather than in the neurons in PD.

There is some loss of dopamine function in MSA because the Parkinsonian form does damage the substantial nigra, but the appearance on the DAT scan is somewhat different because in MSA you can see the damage is still somewhat even, whereas in PD the damage is asymmetric.  So, the DAT scan can give you a clue, but it is not a definitive test to separate the two.

Dr. Bressman says there are papers suggesting an MRI can help to distinguish between the two, but there is a lot of debate about that.  Doctors will sometimes send patients for a glucose PET scan to use the glucose metabolic pattern to distinguish between typical Parkinson’s and more of an atypical parkinsonism of some sort.  The definitive diagnostic method is really to follow patients over time and watch the manifestation of symptoms, responsiveness to medications, and putting all the pieces together.

QUESTION AND ANSWER

Dave Iverson asked the doctors what can be learned about one of these neurodegenerative disorders as we learn about another of them.  Dr. Standaert says they are all age-associated diseases.  While young people do, occasionally, develop neurodegenerative diseases they develop after age 50, 60, 70 and beyond so age is a trigger.  They are all also associated with the development of abnormal proteins.  Each disorder is a different protein (misfolding protein), but at the core there are important commonalities.

Dave Iverson asked if there is an important reason to pursue the right diagnosis.  Dr. Bressman says patients really want to know what it is.  Knowledge is power, and getting the right diagnosis can affect getting the right treatment.  When you get to MSA, PSP, CBD at this point the treatment are empiric for the most part.  It is important in terms of prognosis, family counseling, clinical trials, and ultimately for targeted treatments, when those become available.  We think of PD as being a homogenous entity, but there are subtypes, early onset, those with more or less gait disorder.  So, on the one hand we lump them together, and on the other hand we want to customize treatment to each individual’s greatest difficulties.

Dave Iverson asks if essential tremor can progress to PD.  Dr. Standaert says sometimes doctors will diagnose essential tremor (often symmetrical, runs in families, and is bilateral, so not PD) and the patient will return with real PD symptoms.  People with essential tremor tend to be diagnosed with PD more frequently with PD than the general population.  They thought this was due to misdiagnosis as essential tremor when it is incipient PD.  DAT scan can help with this teasing out between these two conditions.  Dr. Bressman totally agrees.  This lingering question of whether essential tremor increases risk of developing PD, or is essential so common some percentage will go on to develop PD in the same numbers of the general population, or are some number of those diagnosed with PD misdiagnosed until the PD symptoms become obvious.  That’s why we have the DAT scan.  That’s what it is FDA approved for, to distinguish between these conditions.  Dr. Standaert says if there is a mechanistic or genetic connection between essential tremor and PD, they haven’t discovered it, yet.

Dave Iverson asked if it is unusual for someone to have PD and then ALS, for example.  Dr. Bressman says it is an unlikely but now that we have different genetic subtypes, looking at ALS through a genetics lens, it is a heterogeneous disorder and some people who have motor-neuron disorder can have parkinsonism or a PSP-like picture.  So, the motor neuron picture is getting more complicated as we’re understanding the genetics.  She has had patients with motor-neuron disease and parkinsonism who have turned out to have one of these genetic subtypes.  It’s rare.  They are separate disorders but in some subtypes you can have the two together.

Dave Iverson asked if the LRRK2 mutation that causes the most common genetic form of PD can also lead to other movement disorders.  Dr. Standaert says in families where the original LRRK2 gene was discovered as a cause of PD (2-4% of cases in the US) some individuals had MSA or PSP (tau) -looking pathology.  So there were other forms of neurodegenerative disease in those families.  This indicates LRRK2 can not only trigger PD, but other forms of neurodegenerative diseases.  Researchers wonder about LRRK2 — does something happen far upstream, modulating the response of the brain to these mis-folded proteins, perhaps modulating the inflammatory response that follows them.  So, is it a general kind of gene that can enable a number of different pathologies?

Dr. Bressman has been looking for gene carriers that have these other neurodegenerative disorders or other phenotypes, but hasn’t found that so far.   Family members who are gene carriers are either normal (healthy) or have PD, although it is classic PD.  There is more of a gait/balance issue than a tremor.  Some have a classic rest tremor.  They haven’t identified motor-neuron disease or PSP or other neurologic pictures in these families.  Only 28-35% of people who have this gene will develop PD before age 80.  This seems to lead to a connection between a link between the gene and some upstream event, or some sort of exposure to lead to PD.

Dr. Standaert says most disease process are a combination between genetics and environment.  We just don’t understand this enough in PD.

Dave Iverson asked Alexander if he has autonomic symptoms (bladder, constipation, blood pressure, etc.).  Alexander says yes, he didn’t realize that they were associated to his illness until the doctor confirming LBD started asking him about some autonomic issues, specifically.  Then he knew all his symptoms were related.

Dave Iverson asked Dr. Bressman if these autonomic symptoms cut across all these disorders?  She says certainly PD and MSA and can be the most debilitating feature (like low blood pressure, and bladder issues).

Alexander comments (and the doctors both agree) that proper diagnosis is important, especially for those with LBD, because word needs to get out to doctors, patients and families to prevent patients being given neuroleptics (such as Haldol) which are powerful blockers of the dopamine receptors in the brain.  These types of drugs are used widely in medicine when someone has hallucinations (common in LBD).  If you give this to someone with LBD, even though they may not have symptoms that manifest as parkinsonian/movement related, they can become rigid and stiff for weeks.

Dave Iverson asked what is the difference in prognosis between these different disorders.  Alexander says his doctor says, in his experience, the rate at which the initial condition unfolds is similar to the rate at which it further progresses.  If symptoms come on gradually, it is likely to continue to progress just as slowly and is unlikely to make sharp downturns.  That is good news for him as his took so long to diagnose.

Dr. Standaert agrees, although no two cases are exactly the same.  The pace of one’s disease progression doesn’t change a lot over time.  These neurodegenerative disorders progress at different rates from each other, ALS tends to progress much more rapidly than others.

Dr. Bressman agrees.  There is no crystal ball because something new can happen as one ages.

Dave Iverson asked Dr. Bressman to talk about dystonia.  She says dystonia is on the list separately because a not insignificant percentage of PD, particularly with early onset, can be caused by the disease itself or medication induced.  How you treat it depends on what you think is the cause (peak dose, end of dose, early morning) so you may adjust the timing, Amantadine, or Entacapone.  Ultimately, the best treatment will be better dopaminergic meds, DBS or a cure.

Dave Iverson asked if exercise helps in all of these disorders as it does for PD.  Dr. Standaert thinks exercise is helpful in all of them, but in PSP there is a tremendous issue with balance and falling.  MS is worsened by overheating, so be careful with that.  Apply the right kind of exercise for safety to each disorder.  Alexander says he only recently realized exercise is helpful for him.

Dave Iverson asked if there is a connection in both MS and ALS.  Dr. Standaert says both have abnormal proteins, but the part of the brain attacked is different.  MS is quite different as it is an immune attack upon the brain, but the commonality is the recent recognition of the inflammation response between all these disorders.  Otherwise, the cause, diagnosis, and management is quite different.

Dave Iverson asks about the more drastic drop in blood pressure between in MSA than in PD.  Dr. Bressman says that is true.  The treatments are very similar, but too many patients don’t talk about it.  If they are feeling faint they should tell their doctor and have regular blood pressure checks to discuss how to manage it.  Its dangerous because it can lead to falling, but there are a lot of treatment options.  Some people are even still on old blood pressure meds to lower blood pressure from cardiologists prior to adding a neurodegenerative disorder, and those aren’t needed anymore.

Dave Iverson asks Dr. Bressman if she is hopeful that connections between research will lead to treatments across all these disorders.  She is quite hopeful and the research is broad and applicable to not only insight into PD, but other disorders with respect to the search for a cure or better uses of the treatments they already have.

Dave Iverson asks Dr. Standaert if he things that is encouraging for pharmaceutical companies.  He says the more they learn about these diseases the more they realized there are shared commonalities of attack to research treatments.  Success in one will really open the door to success in others.  The rare disorders may not get the funding for research, but will benefit from those getting funding.  PD may not be just one condition because there are more than one gene that can trigger it, and a multitude of symptoms.  Dr. Bressman says one type of ALS may share a treatment option with some type of PD.

Dave Iverson asks Alexander to close the conversation.  Alexander says he has found with respect to his hallucinations is to use them as creative prompts for writing poetry and other creative works.  That is always potentially possible and there is more attention to this in the dementia care community.