End of Life: Helping with Comfort and Care

I’m on the National Institute on Aging’s email alert list for new publications from the NIA.** This week, I received an alert about a new publication on “End of Life.” Chapters include: Providing Comfort at the End of Life, Finding Care at the End of Life, Dementia at the End of Life, Understanding Health Care Decisions, What Happens When Someone Dies, Things to Do After Someone Dies, Getting Help for Your Grief, and Planning for End-of-Life Care Decisions. You can download the publication online, read it online, or order a (free) print copy. Here’s the information I received:

NEW from the National Institute on Aging!
“End of Life: Helping with Comfort and Care”

Providing Comfort at the End of Life with Help from the National
Institute on Aging

When someone close to us is nearing the end of life, there may be
many questions. How can I offer comfort and support? Is there one
“best” place for caregiving? Are there some approaches to making
decisions that can be helpful? Do people with dementia have special
needs at the end of life? End of Life: Helping with Comfort and Care,
a new publication from the National Institute on Aging (NIA), part of
the National Institutes of Health (NIH), can help answer these
questions and others.

Older people need increasingly more care as they near the end of
life. Families and friends want to provide comfort, but may not know
what to do or say. This new publication can help. Written in a
compassionate tone, End of Life: Helping with Comfort and Care
features large print, helpful questions to ask, and resources for
those who want to learn more.

To preview, download or print End of Life: Helping with Comfort and
Care, go to:
www.nia.nih.gov/HealthInformation/Publi … /endoflife

You can also order a free print copy:

Order online at:
www.nia.nih.gov/HealthInformation/Publi … /endoflife

Call the NIA Information Center at 1-800-222-2225, OR
E-mail us at [email protected].
[Robin’s note: the phone is answered and emails are replied to M-F 9-5. You can leave a message after hours.]

Please pass the word to others who may be interested!

The staff of the National Institute on Aging Information Center

** Robin’s note: You can receive these alerts as well by clicking on “Sign up for Email Alerts” on this webpage http://www.nia.nih.gov/Alzheimers/ — this is the AD Education and Referral Center’s webpage.

Neuropathologic criteria for corticobasal degeneration (CBD)

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.



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.

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)

A call to rename PSP to “Richardson’s Disease”

One of my PSP researcher heroes is Dr. David Williams, formerly with the University College of London and now at an Australian university. He’s the lead author on this article. The second author is Dr. Andrew Lees who is the head of the PSP Europe Association, based in London. The final author is Dr. John Steele, one of the “discoverers” of PSP. At the Society’s PSP research symposium I attended in November ’07, Dr. Steele said that he wanted “PSP” renamed to “Richardson’s Disease,” after Dr. Clifford Richardson, one of the other “discoverers” of PSP. (Dr. Steele is the first speaker in “The Physicians Guide to PSP” at https://www.psp.org/materials/ne_dvd_final.html; he describes the neurological exams conducted by Dr. Richardson in the late 50s with various patients captured on video.)

In this article in the journal Neurology, the authors “propose that the classic clinical presentation of PSP-tau pathology be renamed Richardson’s disease, and that the commonest clinical variant be termed PSP-parkinsonism.”

I’ll copy the abstract below.


Neurology. 2008 Feb 12;70(7):566-73.

J. Clifford Richardson and 50 years of progressive supranuclear palsy.

Williams DR, Lees AJ, Wherrett JR, Steele JC.
Faculty of Medicine, Monash University, Alfred Hospital Campus, Melbourne, Australia

OBJECTIVE: To trace the historical events leading to Richardson’s clinical description of progressive supranuclear palsy (PSP) in the context of subsequent observations of its clinical heterogeneity and pathologic overlap with other tauopathies.

BACKGROUND: Fifty years ago, Canadian neurologist J. Clifford Richardson identified patients in Toronto with a syndrome of supranuclear vertical gaze palsy, pseudobulbar palsy, axial rigidity-in-extension, and cognitive impairment. In his seminal description, Richardson predicted that further clinicopathologic observations would broaden the clinical syndrome and that this was unlikely to be a disorder restricted to the Toronto region.

METHODS: The recollections of two of Richardson’s contemporaries and archival material from his time were used as primary materials. Publications that follow the evolution of his observations were examined.

RESULTS: Recent factor analysis of pathologically verified PSP cases has confirmed the accuracy and uniformity of the original classic clinical description of PSP and vindicated Richardson’s prediction of clinical variants. Most notably, a presentation with Parkinson syndrome and absent gaze palsy has been identified, with less severe PSP-tau pathology.

CONCLUSIONS: In recognition of his seminal observations, we propose that the classic clinical presentation of PSP-tau pathology be renamed Richardson’s disease, and that the commonest clinical variant be termed PSP-parkinsonism.

PubMed ID#: 18268249 (see pubmed.gov for abstract only)

FDA Warning on Botox (2/8/08)

This may of interest to those using botox to treat dystonia and contractures. I read about this FDA warning from Friday on an MSA-related online discussion group today.

Here’s the FDA warning to the public: (it’s short)


February 8, 2008

Consumer Inquiries:

FDA Notifies Public of Adverse Reactions Linked to Botox Use
Ongoing safety review of Botox, Botox Cosmetic and Myobloc taking place

The U.S. Food and Drug Administration today notified the public that Botox and Botox Cosmetic (Botulinum toxin Type A) and Myobloc (Botulinum toxin Type B) have been linked in some cases to adverse reactions, including respiratory failure and death, following treatment of a variety of conditions using a wide range of doses.

In an early communication based on the FDA’s ongoing safety review, the agency said the reactions may be related to overdosing. There is no evidence that these reactions are related to any defect in the products.

The adverse effects were found in FDA-approved and nonapproved usages. The most severe adverse effects were found in children treated for spasticity in their limbs associated with cerebral palsy. Treatment of spasticity is not an FDA-approved use of botulism toxins in children or adults.

The adverse reactions appear to be related to the spread of the toxin to areas distant from the site of injection, and mimic symptoms of botulism, which may include difficulty swallowing, weakness and breathing problems.

The FDA is not advising health care professionals to discontinue prescribing these products.

The agency is currently reviewing safety data from clinical studies submitted by the drugs’ manufacturers, as well as post-marketing adverse event reports and medical literature. After completing a review of the data, the FDA will communicate to the public its conclusions, resulting recommendations, and any regulatory actions.

The notification is in keeping with the FDA’s commitment to inform the public about its ongoing safety reviews of drugs. The early communication, which includes background information and advice for health care professionals, can be viewed at: http://www.fda.gov/cder/drug/early_comm … toxins.htm

And here’s info for healthcare professionals: (it’s understandable)

http://www.fda.gov/cder/drug/early_comm … toxins.htm

Early Communication about an Ongoing Safety Review
Botox and Botox Cosmetic (Botulinum toxin Type A) and
Myobloc (Botulinum toxin Type B)

This information reflects FDA’s current analysis of available data concerning these drugs. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug products and the emerging safety issue. Nor does it mean that FDA is advising healthcare professionals to discontinue prescribing these products. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. FDA intends to update this document when additional information or analyses become available.

FDA has received reports of systemic adverse reactions including respiratory compromise and death following the use of botulinum toxins types A and B for both FDA-approved and unapproved uses. The reactions reported are suggestive of botulism, which occurs when botulinum toxin spreads in the body beyond the site where it was injected. The most serious cases had outcomes that included hospitalization and death, and occurred mostly in children treated for cerebral palsy-associated limb spasticity. Use of botulinum toxins for treatment of limb spasticity (severe arm and leg muscle spasms) in children or adults is not an approved use in the U.S.

These serious systemic adverse reactions occurred following treatment of a variety of conditions using a wide range of botulinum toxin doses. FDA is currently reviewing safety data from clinical studies submitted by the manufacturers of Botox, Botox Cosmetic and Myobloc, as well as post-marketing adverse event reports and the medical literature.

Botox (botulinum toxin type A) is approved for treatment of conditions such as blepharospasm (spasm of the eyelids), cervical dystonia (severe neck muscle spasms), and severe primary axillary hyperhydrosis (excess sweating). Botox Cosmetic, also botulinum toxin Type A, is approved for temporary improvement in the appearance of moderate to severe facial frown lines.

Myobloc (botulinum toxin Type B) is approved for the treatment of adults with cervical dystonia; the safety and effectiveness of Myobloc for cervical dystonia in children have not been established.

FDA is aware of the body of literature describing the use of botulinum toxins to treat limb spasticity in children and adults. The safety, efficacy and dosage of botulinum toxins have not been established for the treatment of limb spasticity of cerebral palsy or for use in any condition in children less than 12 years of age.

The current prescribing information (labeling) for Botox, Botox Cosmetic and Myobloc describes adverse reactions occurring in regions near the site of injection for each product’s approved uses, such as dysphagia (difficulty swallowing) after injections to treat cervical dystonia, or ptosis (drooping eye lids) after injections for glabellar frown lines or for strabismus and blepharospasm.

The Warnings sections of the labeling for both botulinum toxin products note that important systemic adverse effects, including severe difficulty swallowing and difficulty breathing have occurred in patients with neuromuscular disorders after local injection of typical doses of botulinum toxin. FDA now has evidence that similar, potentially life-threatening systemic toxicity from the use of botulinum toxin products can also result after local injection in patients with other underlying conditions such as those with cerebral palsy associated limb spasticity. Systemic toxicity has been reported in children, several of whom required feeding tubes and/or ventilation (breathing) support.

Until such time that FDA has completed its review, healthcare professionals who use medicinal botulinum toxins should:

* Understand that potency determinations expressed in “Units” or “U” are different among the botulinum toxin products; clinical doses expressed in units are not comparable from one botulinum product to the next

* Be alert to the potential for systemic effects following administration of botulinum toxins such as: dysphagia, dysphonia, weakness, dyspnea or respiratory distress

* Understand that these effects have been reported as early as one day and as late as several weeks after treatment

* Provide patients and caregivers with the information they need to be able to identify the signs and symptoms of systemic effects after receiving an injection of a botulinum toxin

* Tell patients they should receive immediate medical attention if they have worsening or unexpected difficulty swallowing or talking, trouble breathing, or muscle weakness

What does FDA know now about these data?

The FDA has reviewed post-marketing cases from its Adverse Event Reporting System (AERS) database and from the medical literature of pediatric and adult patients diagnosed with botulism following a local injection with a marketed botulinum toxin product.

The pediatric botulism cases occurred in patients less than 16 years old, with reported symptoms ranging from dysphagia to respiratory insufficiency requiring gastric feeding tubes and ventilatory support. Serious outcomes included hospitalization and death. The most commonly reported use of botulinum toxin among these cases was treatment of limb muscle spasticity associated with cerebral palsy. For Botox, doses ranged from 6.25 to 32 Units/kilogram (U/kg) in these cases. For Myobloc, reported doses were from 388 to 625 U/kg.

The reports of adult botulism cases described symptoms including patients experiencing difficulty holding up their heads, dysphagia and ptosis. Some reports described systemic effects that occurred distant from the site of injection and included weakness and numbness of the lower extremities. Among the adult cases that were serious, including hospitalization, none required intubation or ventilatory support. No deaths were reported. The doses for Botox ranged from 100 to 700 Units and for Myobloc from 10,000 to 20,000 U.

This early communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs. FDA will communicate to the public its conclusions, resulting recommendations, and any regulatory actions after the review of the data are completed.

Report serious adverse events to FDA’s MedWatch reporting system by completing a form on line at http://www.fda.gov/medwatch/report/hcp.htm, by faxing (1-800-FDA-0178), by mail using the postage-paid address form provided online (5600 Fishers Lane, Rockville, MD 20853-9787),
or by telephone (1-800-FDA-1088)