Category Archives: CBD

On the horizon? – lithium study in PSP

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In January ’07, Glenn, a member of the CBD-related Yahoo!Group reported on a trip with his mother (diagnosed with CBD) to Mayo Rochester. Contained in one of the posts (2/3/07) is short mention of lithium:

“Lithium — They had high hopes for lithium because it so effectively
blocked GSK-3B in the lab, but it blocks a number of other things as
well. Mayo had ten patients on lithium and they all elected to cease
treatment because the side effects were so bad.”

Glenn’s father accompanied his mother to Mayo Rochester in Feb ’08. Yesterday Glenn posted a report on his visit. His father raised the topic of lithium with the Mayo Rochester MD:

“The main thing my father wanted to consult with them about was lithium. He has been reading the literature that points to lithium as a potent tau inhibitor. A very recent study released last month showed lithium halting and even reversing some of the tau damage in one of the first human trials. (I have not yet found this study online–I will forward it when I find it.) The Mayo docs said that the study was highly significant (“blockbuster” was the word they used). This backs up what the animal models have been showing in other studies. My father had been talking to a psychiatrist in Pittsburgh who frequently prescribes lithium for bipolar disorder and has gotten very good at monitoring patients who take the drug. In the case of bipolar disorder, the downsides of lithium must not be worse than the downsides of being bipolar. However, the Mayo docs confessed, that neurologists have never much cared for lithium. ‘Psychiatrists put people on lithium and neurologists take them off,’ he said, because of other neurological side-effects lithium can create. The have had a few CBD patients try lithium, but none of them stayed on it very long. However, the Mayo docs were very aware of the increasing evidence in favor of lithium. To be sure, not every study shows it having a dramatic effect, but there is enough evidence there to try it. Not many people have tried it for CBD or even Alzhiemers, and maybe the key to treatment is close monitoring of the drug dosage and effects.

So here is what my parents are planning to do: The doc at Mayo will be working with the ‘lithium-literate’ psych in Pittsburgh and my mother’s local neurologist as well. They will work out a plan for starting her on lithium and tracking her progress. This involves starting with very low doses, then working up until the side-effects are bad and then backing off. I assume they will be running other tests during the treatment as well. We’ll see how it goes!

In other news, I mentioned last year that Mayo was working on another potentially potent tau-blocking drug. They said that the main researcher for the drug is now working with Merck and has access to their resources to bring the drug to market. No idea what kind of timeframe, of course.

They recently began deep brain stimulation on another CBD patient and the jury is still out. It seems to be helping a little, but the location and amount of stimulation are crucial to effective treatment, so it could take some experimentation to get it right.”

I don’t know anything about the tau-blocking drug. This would be useful in AD, PSP, and CBD — all tauopathies. As some of you see MDs at Mayo Rochester, please ask about this during your next appt!

About the exciting lithium study recently published, I did a PubMed search yesterday and couldn’t find anything on lithium and PSP, CBD, or tau published in late ’07 or early ’08. I will try to follow up with a Mayo Rochester MD on this. As some of you see MDs at Mayo Rochester, please ask about this during your next appt!

I’ve been emailing the PSP expert, Dr. Lawrence Golbe, about lithium for many months. (He writes an “Ask the Doctor” column in the CurePSP Magazine.) I finally heard this from him today. Apparently on the horizon is an NIH-funded study of lithium in PSP patients. Here’s his very short email:

“There is no PI yet. There will be 10 sites in the US, Canada and UK and they have not yet been chosen. It will be 28 weeks of treatment with no placebo group.”
(PI = principal investigator)

I’ll update you when I get more info. Could you all please do the same!?

Robin

Neuropathologic criteria for corticobasal degeneration (CBD)

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As some of you know, I’ve started helping local support group members and others with making brain donation arrangements.  The neuropathology reports that have been coming back to families are rather challenging to read!

The reports that show the brain donor had corticobasal degeneration (CBD) refer to the neuropathologic criteria for the disorder.  I’ve copied the abstract below.

Robin

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J Neuropathol Exp Neurol. 2002 Nov;61(11):935-46.

Office of Rare Diseases neuropathologic criteria for corticobasal degeneration.

Dickson DW, Bergeron C, Chin SS, Duyckaerts C, Horoupian D, Ikeda K, Jellinger K, Lantos PL, Lippa CF, Mirra SS, Tabaton M, Vonsattel JP, Wakabayashi K, Litvan I; Office of Rare Diseases of the National Institutes of Health.

Abstract
A working group supported by the Office of Rare Diseases of the National Institutes of Health formulated neuropathologic criteria for corticobasal degeneration (CBD) that were subsequently validated by an independent group of neuropathologists. The criteria do not require a specific clinical phenotype, since CBD can have diverse clinical presentations, such as progressive asymmetrical rigidity and apraxia, progressive aphasia, or frontal lobe dementia. Cortical atrophy, ballooned neurons, and degeneration of the substantia nigra have been emphasized in previous descriptions and are present in CBD, but the present criteria emphasize tau-immunoreactive lesions in neurons, glia, and cell processes in the neuropathologic diagnosis of CBD. The minimal pathologic features for CBD are cortical and striatal tau-positive neuronal and glial lesions, especially astrocytic plaques and thread-like lesions in both white matter and gray matter, along with neuronal loss in focal cortical regions and in the substantia nigra. The methods required to make this diagnosis include histologic stains to assess neuronal loss, spongiosis and ballooned neurons, and a method to detect tau-positive neuronal and glial lesions. Use of either the Gallyas silver staining method or immunostains with sensitive tau antibodies is acceptable. In cases where ballooned neurons are sparse or difficult to detect, immunostaining for phospho-neurofilament or alpha-B-crystallin may prove helpful. Methods to assess Alzheimer-type pathology and Lewy body pathology are necessary to rule out other causes of dementia and Parkinsonism. Using these criteria provides good differentiation of CBD from other tauopathies, except frontotemporal dementia and Parkinsonism linked to chromosome 17, where additional clinical or molecular genetic information is required to make an accurate diagnosis.

PubMed ID#: 12430710  (see pubmed.gov for the abstract – it’s free)

“Doctor is touched by…woman’s devotion” to her husband with locked-in syndrome

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Many of us in the PSP and CBD communities feel as though our family members are “locked in.”  This is a sweet article in the LA Times by a physician who was touched by a woman’s devotion in caring for her husband with locked-in syndrome.

Robin

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articles.latimes.com/2007/dec/17/health/he-practice17

IN PRACTICE
In watching a wife tenderly care for her husband, who can blink but can’t move, a doctor is touched by the woman’s devotion.
By Steve Dudley, Special to The Times
December 17, 2007

In a corner of a room he shares with three other residents at the nursing home, a patient with a curious illness stares out the window at an empty bird-feeder.

He holds his arms in a curious, characteristic way — elbows and wrists hyperflexed so that his hands are tucked under his chin, like a child in prayer.

Mr. Fletcher has been bedridden for years. He can’t talk, can only moan. He can’t move other than to blink or shift his gaze. The only sign of responsiveness is that his eyes will sometimes follow stimuli, either of voice or hand movement.

Although he cannot move, his sensations are still intact. This means that Mr. Fletcher can still feel pain like you or I, or have that annoying itch that he cannot scratch. And people like Mr. Fletcher have their reasoning fully intact. They can think, dream, hope and reflect upon their endless prison.

Mr. Fletcher has what is commonly referred to as “locked-in syndrome” — the result, occasionally, of a rare form of stroke, happening viciously and suddenly, often striking down people in the prime of life after head trauma.

In Mr. Fletcher’s case, it happened more slowly. He has supranuclear palsy, a degenerative condition of the central nervous system that usually afflicts the very elderly, although Mr. Fletcher is only in his early 60s. It’s a cousin of Parkinson’s and Alzheimer’s diseases, an insidious condition with symptoms that might start as mild gait abnormalities or difficulty with eye movements and gradually develop over years.

Nobody knows what causes it, and treatments are essentially palliative: You really can’t do a thing for those who suffer from it other than to keep them comfortable.

Mr. Fletcher has been admitted for some rehabilitation as he transitions from the hospital, after a partial bowel obstruction, back to his home. A team of therapists, nurses and aides and, most importantly, his wife, is here to care for him. I suspect that his wife, the one with the least formal training, understands him best.

I’d like to tell you about her.

I am visiting another patient in Mr. Fletcher’s room when Mrs. Fletcher arrives and proceeds to wash him with a moistened towel.

Carefully and tenderly, she alternates between wiping and drying, turning him first one way, then another. Patiently, meticulously and ever so gently, she bathes him.

After she finishes with the bathing, she rubs her husband down with lotion, massaging it into his skin until it is supple. Then the shaving begins. She lathers his face and, with smooth, efficient strokes, manages to remove a three-day growth of stubble. You can see his eyes sparkle as she winds up her ministrations.

I try not to stare. It seems intrusive, to watch them together, intimate, in an interaction almost as private as making love.

She is caring for this man for all she is worth. Being with him, cleaning him, giving of herself to him and receiving at the most a blink or grunt in return.

Now that’s love. That’s commitment. In a time when people get divorced for the most superficial of reasons, it is a tremendous encouragement to see true love in action.

Mr. Fletcher is a handsome black man with beautiful ebony skin. His wife is Vietnamese. I imagine they met during the Vietnam War when he was a dashing GI and she was a scared young woman whose homeland was being split in two.

As I watch her bathe him, I reflect on what their early years together might have been like. Running on the beach, staying out till dawn, picnics, favorite restaurants and lots of dancing — they look like a couple who used to dance a lot.

I read of a young guy over in France, barely in his 40s, who became locked-in after a stroke. He had been a magazine editor. With the patience of Job, he dictated a book by blinking to a scrivener.

He referred to himself as feeling like a captive in a diving bell. One can only imagine the terror and loneliness of being in this state. You’re completely dependent upon others for all your needs, though you cannot voice any of them. Too warm? Too cold? Too bad.

And the people who are there to help often treat you as someone who cannot understand, as if you’re in a coma.

I’ve seen only one other patient who was locked-in, and that was back in medical school. We were on “physical diagnosis” rounds. That’s where a group of sleepy-eyed doctors in training dutifully follow their chief resident all over the hospital looking for interesting cases.

We popped into this guy’s room. I can’t remember his name. For that matter, I don’t know if we were ever told. He was just the interesting case on the eighth floor. As we lined the bed, we were grilled by a supervising resident about the case before us. This drill, known as “pimping,” is endorsed as a useful, hands-on, didactic exercise — and it may serve its purpose, but more commonly it devolves into brash showmanship at best and downright intellectual bullying at worst.

And we were pimped about the poor gentleman who was locked-in. He just lay there, hearing every word we spoke about him.

Not once did anyone address him directly or acknowledge that he was a person of any real worth. He was simply an exercise in learning, a specimen.

As I watch Mrs. Fletcher, I reflect on that experience. I am struck by the contrast between a devoted wife and a group of doctors-in-training making their cursory visit before moving on to the next interesting case.

She is so kind to him, devoted, caring. I suppose that is what the marriage vows mean when they speak of “in sickness and in health.” Here is tangible evidence of someone being faithful to that promise. I’m sure it is way more than she bargained for, but she dispatches her duties willingly, without resentment.

When you’re young, you take your health for granted. Slowly, it is taken away from even the strongest of us. That day, Mrs. Fletcher taught me volumes about the timelessness of love and the gift of health.

Steve Dudley is a family physician in Seattle.

 

 

Applause sign (clap test) – updated research

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Here’s some new research that probably speaks to the results that Dubois got in ’05 when he and other French researchers said that the “applause sign helps to discriminate PSP from FTD and PD.”

This newly-published research looks at those with PD and “various forms of atypical parkinsonism.” (I’ll have to get the full article to know which forms were included.) These Dutch researchers found: “Although the proportion with an abnormal clapping test was significantly higher in atypical parkinsonism, the clapping test did not discriminate well between Parkinson’s disease and atypical parkinsonism.”

Journal of Neurology. 2007 Oct 15; [Epub ahead of print] Diagnostic accuracy of the clapping test in Parkinsonian disorders.

Abdo WF, van Norden AG, de Laat KF, de Leeuw FE, Borm GF, Verbeek MM, Kremer PH, Bloem BR.
Parkinson Centre Nijmegen (ParC), Institute of Neurology, Radboud University Nijmegen Medical Centre, The Netherlands.

BACKGROUND : To determine the diagnostic value of the clapping test, which has been proposed as a reliable measure to differentiate between progressive supranuclear palsy (where performance is impaired) and Parkinson’s disease (where performance should be normal).

METHODS : Our study group included a large cohort of consecutive outpatients including 44 patients with Parkinson’s disease, 48 patients with various forms of atypical parkinsonism and 149 control subjects. All subjects performed the clapping test according to a standardized protocol.

RESULTS : Clapping test performance was normal in all control subjects, and impaired in 63% of the patients with atypical parkinsonism. Unexpectedly, we also found an impaired clapping test in 29% of the patients with Parkinson’s disease.

CONCLUSION : Although the proportion with an abnormal clapping test was significantly higher in atypical parkinsonism, the clapping test did not discriminate well between Parkinson’s disease and atypical parkinsonism.

PubMed ID#: 17934886

The “applause sign” is where you ask someone who might have PSP to clap. While clapping, you tell them to stop. The person with PSP continues to clap; it takes them awhile to stop.

In a study done by Dubois, 30 out of 42 patients diagnosed with PSP could not stop applauding immediately after being told to stop. Interestingly, none of those with FTD or PD had trouble stopping.

Here’s the abstract of the Dubois article (published 6/05 in Neurology):

*Neurology. 2005 Jun 28;64(12):2132-3.

“Applause sign” helps to discriminate PSP from FTD and PD.

Dubois B, Slachevsky A, Pillon B, Beato R, Villalponda JM, Litvan I.
INSERM, Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France.

“Applause sign” helps to discriminate PSP from FTD and PD
The “applause sign” is a simple test of motor control that helps to differentiate PSP from frontal or striatofrontal degenerative diseases. It was found in 0/39 controls, 0 of 24 patients with frontotemporal dementia (FTD), 0 of 17 patients with Parkinson disease (PD), and 30/42 patients with progressive supranuclear palsy (PSP). It discriminated PSP from FTD (p < 0.001) and PD (p < 0.00). The “three clap test” correctly identified 81.8% of the patients in the comparison PSP and FTD and 75% of the patients in the comparison of PSP and PD.

PubMed ID#: 15985587 (see pubmed.gov)

First Steps after a Dementia Diagnosis

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Hurley Elder Care Law offices are based in Atlanta. In the August 2007 issue of their publication “The Elder Issue,” they offer some guidelines for families to follow once a family member has been diagnosed with Alzheimer’s or any dementia type.

Some of the steps families should follow include:

* Organize a family meeting
* Assess your loved one’s abilities
* Learn about Alzheimer’s disease
* Find a good healthcare provider
* Make long term plans
* Create a support network
* Investigate resources for local support

Here’s a copy of the law firm’s advice. Just replace “Alzheimer’s Disease” with whatever disorder of interest to you as I think the guidelines apply to us all.

Robin

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http://www.openmoves.com/accounts/hurley/issue08_0807-online.html#parents_more

Family Caregivers’ Guide to First Steps after a Diagnosis of Alzheimer’s Disease
Hurley Elder Care Law
The Elder Issue
August 2007

Family situations vary tremendously. Sometimes all adult children and the spouse of the person with AD are in agreement as to the next steps to take, but possibilities for family disagreements are many. The cooperation of the person with AD is very important. Sometimes the person with AD is willing to stop driving, sign all of the important legal documents, and accept the care that he or she may need. But often there is resistance to making changes by the person with dementia.

There are concrete steps that family members can take to make the journey smoother. Some of the steps that you can take as a family member of the person with dementia are:

FAMILY MEETING: Arrange for a regular family meeting to discuss all of the issues related to the diagnosis. Discuss the diagnosis with everyone in the family including family members in other cities or states. Talk about what needs to be done now and in the future. Although the responsibilities of various family members will differ, everyone needs to know what is happening. It is a good idea to have one person who will speak for the family on issues related to health care and the same person or a different person who will speak for the family on financial issues. After the family decides the correct person for each responsibility, formal power of attorney forms can be signed. For example, some family members may live in the same city as the person with dementia. It would make logical sense to designate one of those family members with power of attorney for health care since they can go to the doctor’s office with the person with dementia.

FAMILY MEMBER WITH AD: Make a realistic assessment of the abilities of the person with the disease. The family members cannot rely solely on what the person says she or he can do. These actions must be observed first hand. The idea is to give the person with the disease as much as they can reasonably do for themselves, while not making unrealistic demands. Driving, making financial decisions, staying alone, and using the kitchen safely are all examples of issues that need to be examined on a regular basis. As an example, a person with dementia may think that it is still safe to drive the car alone even though she or he may have gotten lost recently.

LEARNING ABOUT AD: Learn all that you can about the disease. Read books, search the Internet, talk with other family caregivers like yourself, and talk to knowledgeable health care providers. One good place to start is the Alzheimer’s Association at www.alz.org and 1-800-272-3900. A very useful book is “The 36 Hour Day: A Family Guide for Persons with Alzheimer’s Disease, Related Dementing Illnesses, and Memory Loss in Late Life” by Nancy Mace & Peter Rabins.

MEDICAL CARE: Find a health care provider with whom you can work. It may be the physician who diagnosed the disease, or it could be a research physician at Wesley Woods of Emory University or another research program. The person you work with should understand the progression of the disease and know the latest information on medications to treat the symptoms. It is very important that someone goes to each physician appointment with the individual suffering from Alzheimer’s disease in order to better understand the disease and the treatment. This is actually true for most people since they cannot remember everything that the doctor told them five minutes later, regardless of whether they have memory impairment or not.

LIFE CARE PLANNING. Make certain that the necessary legal and financial plans are in place. The most important thing that people should consider is how to find, get and pay for good long term care. This includes the need for an evaluation of the assets available, who needs to have access to those assets and what are the alternative means of financing long term care. From the legal document perspective, a review of or putting into place a Durable Power of Attorney, Health Care Power of Attorney and a Will and/or Trust is very important while the individual still has sufficient capacity to make such decisions.

EMOTIONAL SUPPORT: Set up a support system for yourself. Who in your family or among your circle of friends would be the most supportive of you and your family? Work with them in finding the help you need. You may just need to have someone listen to you and provide some relief from care giving. You may want to join a support group sponsored by the Alzheimer’s Association to work through the feelings that you have and to get ideas about how to best care for your family member with AD. Remember that if you burn out as a caregiver, you are no good to anyone, including yourself.

SAFE RETURN: At a minimum, register the person with Alzheimer’s disease in Safe Return. This is a program of the Alzheimer’s Association that consists of a national registry and an identification bracelet. The cost for Safe Return is $40.00 for the first year and $20 for each year your relative is in the program. With changing technology, there are more and more options available for people to locate a lost or wandering loved one.

RESOURCES TO HELP: Find out about services available in Georgia to assist a person with Alzheimer’s disease. Develop a list of places to contact including adult day, home care agencies, and long term care facilities. Know the services available in your community so you can access these organizations and services as you need them.

CAREGIVER SUPPORT: Take care of yourself. You need to think of yourself as a long-distance runner, not as a sprinter. Pace yourself. Prepare for the long haul. This is not a disease that develops or progresses quickly. Learn to recognize your stress risks and find ways to relieve them. Accept help. Your life and the life of the person with the disease depend upon you caring for yourself.

DIFFICULT SITUATIONS: Difficult situations can easily develop related to family members with Alzheimer’s disease. One example is when the spouse or adult children will not take the keys away from the person with AD, nor will they admit that there are safety issues involved because they themselves are in denial. People in certain stages of the disease cannot make rational decisions. Remember that and take action to protect not only your family member, but the public at large. Another frequently occurring situation happens when one spouse has Alzheimer’s disease and the other spouse has physical health problems. In this circumstance, the husband and wife need different kinds of care and may not be able to stay in their home indefinitely. It pays to be prepared for this eventuality.

HELPING CHILDREN AND TEENS. If you are an adult daughter or son caring for a parent with Alzheimer’s disease, it is likely that you have young children or teenagers still living in the home. Children often experience a wide range of emotions when a parent or grandparent has AD. Younger children may be fearful that they will get the disease or that they did something to cause it. Teenagers may become resentful if they must take on more responsibilities or feel embarrassed that their parent or grandparent is “different.” It is important to find out what the emotional needs of your children are and try to meet them.

The diagnosis of Alzheimer’s disease or any related dementia can be very threatening news, but when a spouse and/or adult children are willing to deal with the illness in a systematic manner, family conflicts can be minimized and the quality of life of the person with the disease can be maximized. The most important thing to do is to take action and take action quickly. The sooner that action is taken, the more options there are available.