Monthly Archives: August 2015

Falls and Dysphagia (new publication co-authored by BSN)

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This post will be of interest to those dealing with falls and/or dysphagia (swallowing difficulty).

Local support group member Phil Myers and I co-authored a case study on falls and dysphagia in the latest issue of the Association of Frontotemporal Degeneration (AFTD) newsletter.  The case study is about “Jackie Riddle” — a composite of my father’s PSP symptoms (confirmed through brain donation) and Phil’s wife Jackie’s PSP symptoms (also autopsy-confirmed).  Though “Jackie Riddle” had PSP, since the focus of the case study is on falls and dysphagia, all of our BSN group members, regardless of diagnosis, will find something of value here.

The newsletter is written for healthcare professionals but I’m fairly certain the language is understandable.  We assumed that healthcare professionals are completely un-knowledgeable about PSP, fall prevention, and treatment of dysphagia.

There are also sections in the newsletter specifically for healthcare professionals working at care facilities.  So if any of you has a loved one in a care facility, those sections may be particularly helpful for staff.

The last two pages of the newsletter are my ideas for practical things that can be done about falls and dysphagia.  Again, though it’s titled “in PSP,” these ideas apply to all four disorders in our BSN group.

Check it out; it’s hot off the presses:

www.theaftd.org/wp-content/uploads/2015/07/PinFTDcare_Newsletter_summer_2015.pdf

Robin

Therapeutic advances and research update in MSA and PSP

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This post may be of interest to those wanting to know about what key research in PSP and MSA has taken place in the last few years, and what research is ongoing or recruiting.

This review article on PSP and MSA clinical trials was just published last week.  The article is written for MSA and PSP researchers, explaining how trials since 2013 have been conducted and highlighting priority areas for future therapeutic research.  The lead author is Werner Poewe, MD, an Austrian physician and researcher.  I believe at the most recent Movement Disorder Society meeting in San Diego, he led a discussion with MSA researchers.  Perhaps he reviewed his article at the meeting.

The article notes that an earlier study of riluzole in MSA and PSP proved the feasibility of conducting large controlled trials in these two disorders.  And the study validated disease-specific rating scales for MSA and PSP.  Nearly 800 subjects were enrolled in that study.  The results, published in 2009, were negative for the medication itself.

But that large riluzole study kicked off other trials — two large clinical trials in MSA (rasagiline, rifampicin) and two large clinical trials in PSP (tideglusib, davunetide).  Those four trials failed as well.  The authors describes those trials in detail.

The article lists all of the other trials conducted since 2013 in PSP and MSA, whether results were published or not.  These include a lithium trial in MSA, two droxidopa trials in MSA, a fluoxetine trial in MSA (unpublished), a high-dose CoQ10 trial (2400mg/day) in PSP, and a valproic acid trial in PSP (unpublished).  Unfortunately one rasagiline study in PSP failed to enroll the necessary number of participants.

Though the therapeutic agents being tested in these trials failed, the studies themselves “have made important contributions to our ability to refine designs in future clinical studies targeting these conditions. As a whole they have shown that enrolling sufficient numbers of patients into trials of the less common forms of degenerative parkinsonism is feasible and that this can be accomplished within reasonable time frames.”

The authors note that despite recent trials in PSP and MSA, “there is still a profound lack of symptomatic trials for these disorders.”

The authors state:  “Although autonomic dysfunction is a key driver of disability in MSA, new drugs to treat OH, such as droxidopa, have not been tested in trials specifically enrolling MSA cases only. Likewise, none of the non-pharmacological measures such as exercise-based approaches that are a central part of palliative therapy for patients with MSA or PSP have been tested in properly designed clinical trials.”

The authors call for future research to address two main areas of need:  “improving symptomatic control, independence and well-being of patients by symptomatic interventions, and altering the course of disease by interfering with the mechanisms underlying progressive neurological impairment and disability.”

In case you are interested in exploring the ongoing trials or trials not yet recruiting in MSA and PSP, see the following list:  (If a trial is recruiting, I’ve listed the NIH clinical trial number so that you can look up info on clinicaltrials.gov)

MSA

  • two for droxidopa (one recruiting, NCT02071459, and one isn’t)
  • autologous mesenchymal stem cells (not recruiting)
  • EGCG – a green tea extract (recruiting, NCT02008721)
  • water/peudoephedrine (recruiting, NCT02149901)
  • AFFITOPE – active immunization against alpha-synuclein (recruiting, NCT02270489),
    nebivolol (not recruiting)
  • AZD3241 (the paper says not recruiting but it’s now recruiting, NCT02388295)

PSP

  • bone marrow stem cell therapy (ongoing, NCT01824121)
  • TPI-287 (ongoing, NCT02133846)

I think most of you will want to stop reading here.  Below, I’ve provided the abstract.

Robin

Abstract

Movement Disorders. 2015 Jul 30.
Therapeutic advances in multiple system atrophy and progressive supranuclear palsy.
Poewe W, Mahlknecht P, Krismer F.

Abstract
Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are relentlessly progressive neurodegenerative diseases leading to severe disability and ultimately death within less than 10 y. Despite increasing efforts in basic and clinical research, effective therapies for these atypical parkinsonian disorders are lacking. Although earlier small clinical studies in MSA and PSP mainly focused on symptomatic treatment, advances in the understanding of the molecular underpinnings of these diseases and in the search for biomarkers have paved the way for the first large and well-designed clinical trials aiming at disease modification. Targets of intervention in these trials have included α-synuclein inclusion pathology in the case of MSA and tau-related mechanisms in PSP. Since 2013, four large randomized, placebo-controlled, double-blind disease-modification trials have been completed and published, using rasagiline (MSA), rifampicin (MSA), tideglusib (PSP), or davunetide (PSP). All of these failed to demonstrate signal efficacy with regard to the primary outcome measures. In addition, two randomized, placebo-controlled, double-blind trials have studied the efficacy of droxidopa in the symptomatic treatment of neurogenic orthostatic hypotension, including patients with MSA, with positive results in one trial. This review summarizes the design and the outcomes of these and other smaller trials published since 2013 and attempts to highlight priority areas of future therapeutic research in MSA and PSP.

© 2015 International Parkinson and Movement Disorder Society.

PMID:  26227071

 

“Could a vitamin or mineral deficiency be behind your fatigue?” (short article, Harvard)

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Fatigue can be a symptom in all of the disorders in our local support group.  Today’s Healthbeat email from the Harvard Medical School points to one mineral and two vitamin deficiencies that may cause fatigue.  It might be worth having an MD check one’s vitamin levels to rule these out as problems if fatigue is present.

Robin

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Excerpts from

Could a vitamin or mineral deficiency be behind your fatigue?

Healthbeat
Harvard Medical School
August 1, 2015

The world moves at a hectic pace these days. If you feel like you’re constantly running on empty, you’re not alone. Many people say that they just don’t have the energy they need to accomplish all they need to. Sometimes the cause of fatigue is obvious — for example, getting over the flu or falling short on sleep. Sometimes a vitamin deficiency is part of the problem. It might be worth asking your doctor to check a few vitamin levels, such as the three we’ve listed below.

* Iron. Anemia occurs when there aren’t enough red blood cells to meet the body’s need for oxygen, or when these cells don’t carry enough of an important protein called hemoglobin. Fatigue is usually the first sign of anemia. A blood test to measure the number of red blood cells and amount of hemoglobin can tell if you have anemia. The first step in shoring up your body’s iron supply is with iron-rich foods (such as red meat, eggs, rice, and beans) or, with your doctor’s okay, over-the-counter supplements.

* Vitamin B12. Your body needs sufficient vitamin B12 in order to produce healthy red blood cells.  So a deficiency in this vitamin can also cause anemia. The main sources of B12 are meat and dairy products, so many people get enough through diet alone. However, it becomes harder for the body to absorb B12 as you get older, and some illnesses (for example, inflammatory bowel disease) can also impair absorption. Many vegetarians and vegans become deficient in B12 because they don’t eat meat or dairy. When B12 deficiency is diet-related, oral supplements and dietary changes to increase B12 intake usually do the trick. Other causes of B12 deficiency are usually treated with regular injections of vitamin B12.

* Vitamin D. A deficit of this vitamin can sap bone and muscle strength. This vitamin is unique in that your body can produce it when your skin is exposed to sunlight, but there also aren’t many natural food sources of it. You can find it in some types of fish (such as tuna and salmon) and in fortified products such as milk, orange juice, and breakfast cereals. Supplements are another way to ensure you’re getting enough vitamin D (note that the D3 form is easier to absorb than other forms of vitamin D).

Local Case – Man Diagnosed with MSA During Life But X-ALD Upon Brain Donation

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This email may be of most interest if you are dealing with MSA that began younger than average with atypical symptoms.  Or if you are interested in what can be learned from post-mortem studies of brains of people diagnosed with MSA while alive.

This article in the journal Neuropathology was published yesterday.  I’m certain it is about a local support group member whose husband supposedly had MSA but, upon brain donation, it was identified that he had a very rare disorder called X-linked adrenoleukodystrophy (X-ALD).  This is the same disorder as the child in Lorenzo’s Oil had.   I believe this disease may be inherited but the donor had no living relatives to investigate.  Note that there is no treatment for adult-onset X-ALD.

The donor had neurological symptoms for over 30 years, and died last year at the age of 69.  The last several years of his life, he was diagnosed with MSA because of cerebellar ataxia, gait problems, speech problems, and autonomic dysfunction.  “A diagnosis of X-ALD was never entertained during his life. He had long disease duration (35 years) and lacked characteristic MRI findings of X-ALD (and of MSA).”

There are only 33 other cases of cerebello-brainstem dominant X-ALD reported worldwide.  Most of the other cases had a family history of X-ALD or Addison’s Disease, adrenal insufficiency or T2-weighted hyperintensities in certain brain areas on MRI.  Our local support group member’s husband had none of these characteristics.  In his case, the “T2 signal abnormalities were interpreted as being due to microvascular pathology common in aging.”  Note that most of the other cases are from Japan and South Korea.

Despite the rarity of X-ALD, the researchers argue that X-ALD should be considered as a differential diagnosis in MSA, especially in younger patients with atypical symptoms.  This sounds like a red herring to me, but I’m anxious to ask some neurologists about this idea.

The Discussion section of the article is interesting in that it reviews details and comparisons of the 34 confirmed X-ALD cases.  I think this is enough for most of you but if you want more, check out the full article.  I’ve also copied the abstract below.

Robin

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Neuropathology. 2015 Jul 31.Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review.

Ogaki K, Koga S, Aoki N, Lin W, Suzuki K, Ross OA, Dickson DW.

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy-confirmed cases exceedingly rare. We report a 69-year-old White man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X-ALD or Addison’s disease. His initial symptom was temporary loss of eyesight at age 34 years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69 years with a diagnosis of MSA. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS-positive, CD68-positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting the optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft-like trilamellar cytoplasmic inclusions in macrophages typical of X-ALD, which prompted genetic analysis that revealed a novel ABCD1 mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello-brainstem dominant form of X-ALD with long clinical course, mild pathological findings, and an ABCD1 p.R163G substitution. We also review a total of 34 cases of adult-onset cerebello-brainstem dominant form of X-ALD. Although rare, X-ALD should be considered in the differential diagnosis of MSA.

© 2015 Japanese Society of Neuropathology.

PMID:  26227820