“Diagnosing and Treating Rapidly Progressive Dementias” (dementia within one year)

Rapidly progressive dementias (RPDs) “include prion diseases such as CJD [Creutzfeldt-Jakob Disease], autoimmune dementias, paraneoplastic conditions, infections that can mimic prion diseases, and fungal infections as well as some viral and toxic metabolic conditions, such as Wernicke’s encephalopathy (a condition that stems from thiamine deficiency often due to malnutrition) and even conditions stemming from complications from an overdose of Pepto-Bismol.”

Here’s a short overview of RPDs. I don’t think it’s necessary to read the entire article, though it is short. For our purposes, here are the key excerpts:

* “Dementia may result from as many as 40 different diseases and conditions ranging from dietary deficiencies to inherited diseases, according to the Encyclopedia of Mental Disorders. With that, the definition of dementia has broadened over time from a focus on memory loss to a focus on impairment in one or more cognitive domains — particularly memory, language, frontal executive function, organizing, planning, and multitasking — that is severe enough to interfere with a person’s daily function. Typically, chronic degenerative dementias are characterized by damage or wasting away of brain tissue usually progressing over seven to 10 years. These include Alzheimer’s disease, frontal lobe dementia, and Pick’s disease. Dementias associated with progression of other diseases or conditions include Huntington’s disease, Lewy body dementia, and other parkinsonian dementias, such as corticobasal degeneration.”

* “Michael Geschwind, MD, PhD, associate professor of neurology at the Memory and Aging Center at the University of California, San Francisco said that although there is no defined time frame for rapidly progressing dementias (RPDs), he uses the term to describe patients that go from normal cognition to dementia within a year or less. However, he has seen some patients with Creutzfeldt-Jakob Disease (CJD) take as long as two years to develop dementia. Although there can be overlap with some typical degenerative dementias presenting in a rapid fashion, in general, patients who may have an RPD need clinicians to consider a different set of disorders, because these conditions can be both treatable and quickly fatal in some cases, Geschwind explained. … In a 2007 monograph on RPD published in Neurology Clinic, Geschwind’s team observed that 15% to 20% of the 825 patients referred to UCSF with rapidly progressing dementia presumed to be CJD turned out to have other non-prion conditions.”

* “Steven Vernino, MD, professor of neurology and neurotherapeutics at the University of Texas Southwestern Medical Center in Dallas, specializes in autoimmune encephalopathies. As a referral center, he said they see a fair number of treatable autoimmune RPDs each year. These include anti-N-methyl D-aspartate (anti-NMDA) receptor antibody encephalitis, paraneoplastic limbic encephalitis (PLE), and autoimmune limbic encephalitis associated with potassium channel-related antibodies, such as leucine-rich, glioma-inactivated 1 (LGI-1) antibody.”

Here’s a link to the full article for those who want to know more:

www.neurologyadvisor.com/neurodegenerative-diseases/diagnosing-and-treating-rapidly-progressive-dementias/article/382447/

Diagnosing and Treating Rapidly Progressive Dementias
Michael O’Leary
Neurology Advisor
November 10, 2014

Robin

Webinar on alpha-synuclein and Lewy bodies

Tomorrow’s Michael J. Fox Foundation “Third Thursday Webinar” may be of interest to you.  It’s from 9am to 10am California time.  The topic is alpha-synuclein protein.  This is the protein involved in Parkinson’s Disease (PD), Multiple System Atrophy (MSA), and Lewy Body Dementia (LBD).  (A different protein is involved with PSP and CBD.)  The webinar will look at research underway to determine if the aggregation of this protein causes diseases and to stop alpha-synuclein from clumping in the brain.

We all have alpha-synuclein protein in our brains.  In PD, the amount of alpha-synuclein in the brain is two or three times the normal amount.

We will also hear the term “Lewy body” on tomorrow’s webinar.  Lewy bodies are the clumps of alpha-synuclein protein that appear in PD and LBD.  Lewy bodies are NOT part of MSA.

If you can’t make the webinar tomorrow due to the time it’s being held but you are interested in the topic, I encourage you to register for the webinar.  Those who register will receive an automatic email indicating when the recording of the webinar is available online.

To find a “Register Now” button and for information on the webinar series, see:
michaeljfox.org/webinars

Robin

Are PET scans helpful in diagnosing dementia?

This is a good post in The Geriatrician, a blog (thegeriatrician.blogspot.com).  The post provides an overview of how a geriatrician thinks about the value of PET scans in diagnosing dementia. Apparently there is very little value so this geriatrician has sent only one to get a PET scan, despite the fact that half of his patients have dementia.

When the author says “PET scans,” he is referring to “FDG PET scans.”  I rather doubt his bottom-line would be any different if he were talking about amyloid PET scans.

The crux of the argument has to do with sensitivity , specificity, positive predictive value, and negative predictive value – statistical terms.  He refers people to Google and Wikipedia to look up definitions of these terms.  He also points to a “handy dandy calculator,” found at vassarstats.net/clin2.html.

The geriatrician says:

“[According] to the Alzheimer’s Association, PET scans to make the diagnosis of dementia are 95% sensitive and 75% specific.  Sensitivity means that if someone has dementia, the test will pick it up. Specificity means that the test doesn’t pick up other things like depression.  … While the sensitivity seems great, the specificity is the achilles heel.”

In the blog post, the geriatrician goes through the math.  In summary, he says:

“I would say that the test is useful as a rule out type of test for those who have an intermediate or low suspicion.  Not so much to make the diagnosis.  I wouldn’t be comfortable telling someone they have a fatal neurodegenerative disease when I have a 20% chance of being wrong.  Or even 8% chance.  The second point is that the test is only useful in the setting of a clinical suspicion.  You can see how the characteristics of the test change depending on clinical suspicion.  However when people talk about PET scans, they imply that maybe it would be useful BEFORE a person has clinical symptoms.  It’s not there yet. Maybe the new Amyloid PET scans but not the tagged glucose pet scans.  After going through the math, this is why I don’t use PET scans.  I think it’s more useful to hone my clinical skills than use a test to compensate for poor clinical skills.”

Read the full blog post here:

thegeriatrician.blogspot.com/2014/11/are-pet-scans-good-enough-to-diagnose.html

Are pet scans good enough to diagnose dementia?
The Geriatrician
Sunday, November 16, 2014

Robin

 

Finding CSF biomarkers for parkinsonian conditions

A terrific article was published recently on CSF (cerebrospinal fluid) biomarkers in parkinsonian conditions such as PSP, CBD (both tauopathies), MSA, DLB, and Parkinson’s Disease (all three are synucleinopathies).  CSF is procured through a lumbar puncture (spinal tap).  Researchers have been looking into whether we can diagnose something with any neurological disorder based on what proteins or compounds are evident in an individual’s CSF.  The thought is that the CSF should reflect what’s going on in the brain.

As the abstract says:

Parkinsonian diseases comprise a heterogeneous group of neurodegenerative disorders, which show significant clinical and pathological overlap. Accurate diagnosis still largely relies on clinical acumen; pathological diagnosis remains the gold standard. There is an urgent need for biomarkers to diagnose parkinsonian disorders, particularly in the early stages when diagnosis is most difficult.

The authors review the strengths and limitations of the most promising CSF markers in parkinsonian conditions.  Here’s a summary of where we are with CSF biomarkers:

Summary Points: CSF Biomarkers in Parkinsonism

Aβ42 has a role in predicting cognitive decline in Parkinson’s disease (PD)

t-α-Syn: most promising marker; differentiates synucleinopathies from other neurodegenerative diseases and controls but is not specific

t-tau and p-tau: inconsistent data, can help differentiate PD from AD and can be useful in combination with other markers

NF-L: useful in differentiating PD from atypical parkinsonian conditions

4R-tau: possible marker of disease progression in PSP

DJ1: potential role in discriminating MSA from PD

Oxidative stress/inflammatory/metabolic markers: promising initial results, requiring further validation

Progress is slow but there is progress.  Perhaps the answers for both alpha-synuclein and tau will come in a combination of imaging and biomarkers.

The full article is available for free from PubMed:

www.ncbi.nlm.nih.gov/pmc/articles/PMC4173749/

Cerebrospinal Fluid Biomarkers in Parkinsonian Conditions: An Update and Future Directions
Nadia Magdalinou, Andrew J Lees, Henrik Zetterberg
Journal of Neurology, Neurosurgery, and Psychiatry. 2014;85(10):1065-1075.

Robin

 

Robin Williams had Lewy Body Dementia

I saw the SF Chronicle article yesterday about the coroner’s report on Robin Williams, age 63.  This short paragraph caught my eye:

“His wife, Susan Schneider, said Williams was dealing with early-stage Parkinson’s disease, and an examination of his brain tissue by UCSF doctors revealed abnormal protein deposits consistent with a form of dementia, the coroner’s report said.”

I believe that Robin Williams was being seen at UCSF (by Georges Naasan, MD) for treatment of Parkinson’s Disease.  And it seems that UCSF autopsied his brain upon death.  (We don’t know if the brain was donated for research or just autopsied. UCSF is not interested in Parkinson’s Disease brains for its brain bank.)

I wondered if the “form of dementia” was Lewy Body Dementia and — some may think perversely — looked around on the web tonight for answers.  It only took a few minutes.

There was a sad article in the NY Daily News indicating that Robin Williams was experiencing RBD (REM sleep behavior disorder) and paranoid delusions, both of which are LBD symptoms.  The article says:

“(Williams) had been having a difficult time sleeping and would sometimes move around a lot in bed or talk loudly in his sleep, which is why he was sleeping in a separate bedroom,” the report stated.

The night before his death, Williams placed several wrist watches in a sock and drove them over to an unidentified recipient’s location because he was “worried about the watches” and wanted to keep them “safe,” the report said.

Finally, we are told what the neuropathologist’s diagnosis is: diffuse Lewy body dementia.  The is the most severe level of Lewy bodies in the brain so it’s surprising that he wasn’t diagnosed with Lewy body dementia prior to his death.

Here’s a link to the NY Daily News article:

www.nydailynews.com/entertainment/gossip/robin-williams-coroner-report-drugs-alcohol-system-article-1.2003220

Robin

 

“How long have I got left?”

This is a New York Times article written by Stanford neurosurgeon Dr. Paul Kalanithi about being diagnosed with advanced-stage lung cancer in 2013.

By the way, one of our local support group members went to undergrad with Paul, and had this to say:  “he is such a warm, intelligent and funny person. I’ve been blown away by his story and how he has handled his diagnosis and shared his insights with the world.  A true gift.”

What first drew me to the NYT article was the discussion about statistics and prognosis.

Many of our local support group members who are caregivers (myself included) want to know how long their loved one has left to live with a neurological disorder.  And many of our local support group members who are those with a neurological diagnosis also want to know how long they have left to live.  Not everyone asks these questions but many do.

In reply, I recite the averages based on published research with confirmed (through brain donation) cases.  But no one can know what an individual’s prognosis is.

It was interesting to read Dr. Kalanithi’s new take on the prognosis question.  After he got a lung cancer diagnosis, he asked the same question of his oncologist:

“But now that I had traversed the line from doctor to patient, I had the same yearning for the numbers all patients ask for. … She flatly refused: ‘No. Absolutely not.’ … At each appointment, a wrestling match began, and she always avoided being pinned down to any sort of number.”

“The path forward would seem obvious, if only I knew how many months or years I had left. Tell me three months, I’d just spend time with family. Tell me one year, I’d have a plan (write that book). Give me 10 years, I’d get back to treating diseases. … My oncologist would say only: ‘I can’t tell you a time. You’ve got to find what matters most to you.'”

Eventually, Dr. Kalanithi has a revised view on the statistics and prognosis question:

“What patients seek is not scientific knowledge doctors hide, but existential authenticity each must find on her own. Getting too deep into statistics is like trying to quench a thirst with salty water. The angst of facing mortality has no remedy in probability.”

As you can probably tell, the entire article is worth reading.  Here’s a link to it:

www.nytimes.com/2014/01/25/opinion/sunday/how-long-have-i-got-left.html

SundayReview | Opinion
How Long Have I Got Left?
New York Times
By Paul Kalanithi
Jan. 24, 2014

Robin

Having a “palliative care conversation”

For the last several years, I’ve been attending the annual Jonathan King lecture at Stanford.  King had cancer and started a lecture series before he died to get across two messages to MDs:

  • they must empathize with their patients
  • they must foster a patient’s feelings of control and hope

This year’s lecture on October 21st was remarkable.  Palliative care expert Timothy Quill, MD, gave a talk about the importance of palliative care.  He said that palliative care is for the seriously ill with “a high symptom burden”, while hospice is for the terminally ill.  In palliative care, there are three thoughts:

  • we hope for the best
  • we attend to the present
  • we prepare for the worst

Dr. Quill noted that all physicians should be able to have a palliative care conversation with their patients.  The conversation includes open-ended questions such as:

  • what is the best that might happen
  • what is the worst that might happen
  • is faith important

Quill believes that “doctors should address the emotional ramifications of illness, as well as the medical treatment plan, with their patients.”

Though Dr. Quill’s lecture was very good, what made the event so remarkable is that he had a palliative care conversation with a Stanford neurosurgeon who was diagnosed last year with advanced-stage lung cancer.  Dr. Paul Kalanithi, the cancer patient, was very open about his thoughts and feelings.  I first read about Dr. Kalanithi in January 2014 as he authored an article in the New York Times about being diagnosed and wondering what his prognosis is.  It was an honor to meet him in person.

Stanford Medicine published an article about Dr. Quill’s conversation with Dr. Kalanithi.  I hope the wonderfulness of the event comes across in the article.  Here’s a link to it:

med.stanford.edu/news/all-news/2014/10/a-conversation-with-a-cancer-patient-facing-the-end-of-his-life.html

A conversation with a cancer patient about palliative care
Stanford Medicine News Center
October 22, 2014

Robin