Monday, December 20, 2004

Amnesia At The Movies: Eternal Sunshine, Memento, and Finding Nemo

Wherein the author finds that the fish gets it right and is pleased with the homage to Patient H.M.:

Sallie Baxendale. Memories aren't made of this: Amnesia at the movies. British Medical Journal 2004; 329: 1480-1483 (18 December). [doi:10.1136/bmj.329.7480.1480]

Full text:

Article [HTML]
Article [.pdf]

Now, where is that ad for the Lacuna Clinic? (grin) After all, Eternal Sunshine is BrainBlog's movie of the year!

Saturday, December 18, 2004

Lunesta (Eszopiclone)

With New Sleeping Pill, New Acceptability?
By ANDREW POLLACK
The New York Times
17 December 2004

Is it a wake-up call for the sleeping pill market? With Wednesday's approval of Sepracor's new drug, Lunesta, a taboo in the use of sleeping pills has been broken. Lunesta is the first sleeping pill whose label will not recommend it be taken for only 7 to 10 days.

[ ... Read the full article ... ] (free registration required)

Friday, December 17, 2004

Mixed Dementia

This week's Journal of the American Medical Association includes a clinical review about current knowledge of dementia in the presence of both probable Alzheimer disease and cerebrovascular disease, including neuropsychological and behavioral information, as well as a discussion of potential medications.
Mixed Dementia: Emerging Concepts and Therapeutic Implications
Kenneth M. Langa, MD, PhD; Norman L. Foster, MD; Eric B. Larson, MD, MPH
JAMA. 2004; 292: 2901-2908.

Context  The prevalence of mixed dementia, defined as the coexistence of Alzheimer disease (AD) and vascular dementia (VaD), is likely to increase as the population ages.

Objectives  To provide an overview of the diagnosis, pathophysiology, and interaction of AD and VaD in mixed dementia, and to provide a systematic literature review of the current evidence for the pharmacologic therapy of mixed dementia.

Data Sources, Study Selection, and Data Extraction  The Cochrane Database of Systematic Reviews was searched using the keyword dementia. MEDLINE was searched for English-language articles published within the last 10 years using the keywords mixed dementia, the combination of keywords Alzheimer disease, cerebrovascular disorders, and drug therapy, and the combination of keywords vascular dementia and drug therapy.

Evidence Synthesis  Dementia is more likely to be present when vascular and AD lesions coexist, a situation that is especially common with increasing age. The measured benefits in clinical trials for the treatment of mixed dementia are best described as statistically significant differences in cognitive test scores and clinician and caregiver impressions of change. In these studies, the control groups’ scores typically decline while the treatment groups improve slightly or decline to a lesser degree over the study period. Nevertheless, even the patients who experience treatment benefits eventually decline. Cholinesterase inhibitor (ChI) therapy for mixed dementia shows modest clinical benefits that are similar to those found for ChI treatment of AD. The N-methyl-D-aspartate (NMDA) antagonist memantine also shows modest clinical benefits for the treatment of moderate to severe AD and mild to moderate VaD, but it has not been studied specifically in mixed dementia. The treatment of cardiovascular risk factors, especially hypertension, may be a more effective way to protect brain function as primary, secondary, and tertiary prevention for mixed dementia.

Conclusions  Currently available medications provide only modest clinical benefits once a patient has developed mixed dementia. Cardiovascular risk factor control, especially for hypertension and hyperlipidemia, as well as other interventions to prevent recurrent stroke, likely represent important strategies for preventing or slowing the progression of mixed dementia. Additional research is needed to define better what individuals and families hope to achieve from dementia treatment and to determine the most appropriate use of medication to achieve these goals.

Wednesday, December 15, 2004

Hoarding Behavior in Brain Damage

From a University of Iowa press release:
Brain Region Identified That Controls Collecting Behavior

[snip]

By studying patients who developed abnormal hoarding behavior following brain injury, neurology researchers in the University of Iowa Roy J. and Lucille A Carver College of Medicine have identified an area in the prefrontal cortex that appears to control collecting behavior. The findings suggest that damage to the right mesial prefrontal cortex causes abnormal hoarding behavior by releasing the primitive hoarding urge from its normal restraints. The study was published online in the Nov. 17 Advance Access issue of the journal Brain.

[snip]

The UI team studied 86 people with focal brain lesions - very specific areas of brain damage – to see if damage to particular brain regions could account for abnormal collecting behavior. Other than the lesions, the patients' brains functioned normally and these patients performed normally on tests of intelligence, reasoning and memory.

[snip]

To determine if certain areas of damage were common to patients who had abnormal collecting behavior, the UI researchers used high-resolution, three-dimensional magnetic resonance imaging to map the lesions in each patient's brain and overlapped all the lesions onto a common reference brain.

"A pretty clear finding jumped out at us: damage to a part of the frontal lobes of the cortex, particularly on the right side, was shared by the individuals with abnormal behavior," Anderson said. "Our study shows that when this particular part of the prefrontal cortex is injured, the very primitive collecting urge loses its guidance.

"This finding sheds some light on a ubiquitous, nearly universal human behavior that we really don't know much about, and we can use this as springboard to think about normal collecting behavior."
[ ... Read the full release ... ]

Friday, December 10, 2004

In The Weeklies

This week's issue of the New England Journal of Medicine (09 December 2004) includes two research papers and one editorial comment on topics concerning Parkinson disease:

Levodopa and the Progression of Parkinson's Disease by The Parkinson Study Group. Abstract

Rivastigmine for Dementia Associated with Parkinson's Disease by M. Emre and colleagues. Abstract

Parkinson's Disease Dementia — A First Step?, an editorial comment by D. Z. Press. Extract

Wednesday, December 08, 2004

Abstract of the Day: Ritalin in Childhood Cancer Survivors

Mulhern RK, Khan RB, Kaplan S, Helton S, Christensen R, Bonner M, Brown R, Xiong X, Wu S, Gururangan S, Reddick WE. Short-term efficacy of methylphenidate: A randomized, double-blind, placebo-controlled trial among survivors of childhood cancer. Journal of Clinical Oncology. 2004 Dec 1; 22(23): 4743-51.

Division of Behavioral Medicine, Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.

PURPOSE: Children surviving acute lymphoblastic leukemia (ALL) and malignant brain tumors (BTs) have a higher incidence of attention and learning problems in school than do their healthy peers. The present study tests the hypothesis that the psychostimulant methylphenidate (MPH) improves cognitive and social functioning among these patients. PATIENTS AND METHODS: We report on 83 long-term survivors of ALL and BT identified as having attentional deficits on behavioral testing and parent or teacher report, and problems with academic achievement. The 47 male and 36 female patients ranged from 0.6 to 14.3 years (median, 5.4 years) of age at diagnosis and 6.7 to 17.9 years (median, 11.9 years) of age at participation. The patients (40 ALL, 43 BT) participated in a randomized, double-blind, 3-week home cross-over trial of placebo (bid), low-dose MPH (0.3 mg/kg; maximum dose, 10 mg bid), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg bid). The primary end points were weekly teacher and parent reports on the Conners' Rating Scales and Social Skills Rating System. RESULTS: Compared to placebo, significant improvement with MPH was reported by teachers and parents on the Conners' Rating Scales and by teachers on the Social Skills Rating System. However, no consistent advantage of moderate dose over low dose was observed. Of those participating, 66 (79.5%) of the 83 patients continued on best clinical management. CONCLUSION: Treatment with MPH can at least temporarily reduce some attentional and social deficits among survivors of childhood ALL and BT. Long-term follow-up will reveal those subsets of patients who are more likely to benefit from MPH.

PMID: 15570081 [PubMed - in process]

Monday, December 06, 2004

"Mind Over Matter" - Wadsworth Center Brain-Computer Interface Project

This evening, the NBC Nightly News ran a feature report entitled "Mind Over Matter," concerning self-control over EEG components to "move" a computer cursor. The research program is the Wadsworth Center Brain-Computer Interface Project in Albany, New York. The report included an interview with the Project's Dr. Jonathan Wolpaw. Information about Dr Wolpaw and the project can be found on this webpage.


What's Happening in Neuroscience?

Yesterday's Sunday magazine in the Boston Globe included a decent feature article about advances in the neurosciences:
Brain Power
By Pamela Ferdinand
The Boston Globe
05 December 2004

[ ... Read the article ... ]

Sickle Cell Clinical Study Halted

Risk of Strokes Halts Sickle Cell Study
By Daniel Yee
Associated Press
The Washington Post
Monday, December 6, 2004; Page A02

ATLANTA, Dec. 5 -- A study aimed at determining whether some children with sickle cell anemia could be weaned off blood transfusion therapy has been halted because two young patients who stopped getting the procedure suffered strokes and others developed a high chance of strokes.

The National Institutes of Health decided to issue a clinical alert recommending that doctors continue with blood transfusions to reduce the risk of stroke among young sickle cell patients, even though the treatment has its own risk.

The study, called Stop II, was funded by the NIH's National Heart, Lung, and Blood Institute and involved 23 U.S. medical centers and two in Canada.

[ ... Read the full article ... ] (free registration required.)

Saturday, December 04, 2004

Business World: Biogen Idec, Elan, & Tysabri

There has been a lot of web searching for information about Tysabri (natalizumab) [formerly Antegren] in the wake of the FDA approval last month for use in multiple sclerosis. A lot of searching has been by patients and concerned family members, clinicians and students, and those interested in the business applications.

I posted a couple of entries about the drug approval that are found in the November archives. I've been looking for a business commentary to note and found one earlier today:

In the business-world end of this, here is an interesting commentary from the 24th of November by a writer for TheStreet.com:

What Price Tysabri?
By Adam Feuerstein
Senior Writer, TheStreet.com
11/24/2004 8:00 AM EST
Read the opinion article

Memory: In Search of What's Lost

From tomorrow's New York Times Sunday Magazine:
In Search of Lost Time
By CATHRYN JAKOBSON RAMIN

The New York Times
Published: December 5, 2004

A few months ago, as I trudged down the stairs of my office building, deep in my thoughts, I noticed a dark-haired woman waving to me from the window of her car. She looked vaguely familiar, but I couldn't place her. Like quite a few others, she had slipped out of my mental Rolodex. In my brain, the synaptic traces that connected us had frayed. Yet again, I had misplaced an entire human being.
[ ... Read the full article ... ]

Julia 1926 (Alzheimer Disease)

jill/txt describes her experience visiting this art display about a woman with Alzheimer disease. Read her blog entry here.

The Julia 1926 website can be found here.

Friday, December 03, 2004

Abstract of the Day: Neuropsychological Assessment

Sarno MT, Postman WA, Cho YS, Norman RG. Evolution of phonemic word fluency performance in post-stroke aphasia. Journal of Communication Disorders. 2005 Mar-Apr; 38(2): 83-107.

Department of Rehabilitation Medicine, School of Medicine, New York University, 400 East 34th Street, New York, NY 10016, USA.

In this longitudinal study, quantitative and qualitative changes in responses of people with aphasia were examined on a phonemic fluency task. Eighteen patients were tested at 3-month intervals on the letters F-A-S while they received comprehensive, intensive treatment from 3 to 12 months post-stroke. They returned for a follow-up evaluation at an average of 10 months post-intervention. Mean group scores improved significantly from beginning to end of treatment, but declined post-intervention. Patients produced a significantly greater number and proportion of modifiers (adjectives and adverbs) between the beginning and end of treatment, with no decline afterwards, implying that they had access to a wider range of grammatical categories over time. Moreover, patients used significantly more phonemic clusters in generating word lists by the end of treatment. These gains may be attributed to the combined effects of time since onset and the linguistic and cognitive stimulation that patients received in therapy. Learning outcomes: Readers of this paper should (1) gain a better understanding of verbal fluency performance in the assessment of aphasia, (2) recognize the importance of analyzing qualitative aspects of single word production in aphasia, and (3) contribute to their clinical judgment of long term improvement in aphasia.

PMID: 15571711 [PubMed - in process]

Progressive Multifocal Leukoencephalopathy

A Brown University press release describes a study published in this week's issue of Science:
Antipsychotic Drugs Stop Fatal Viral Infection In Brain Cells

PROVIDENCE, R.I. -- Generic antipsychotic drugs can protect brain cells from a virus that causes a fatal nervous system disorder, according to research conducted at Brown University and Case Western Reserve University.

The disorder, called progressive multifocal leukoencephalopathy or PML, affects hundreds of Americans with suppressed immune systems, including kidney transplant recipients, cancer patients undergoing chemotherapy and an estimated 4 percent of people with AIDS.

PML is caused by the JC virus, which destroys the cells that produce the fatty sheath that covers nerve cells. This causes dementia, vision loss, movement and speech impairment, paralysis and coma. The disorder is fast moving and fatal; Many patients die within four months after onset. PML is also on the rise. Due to the AIDS pandemic, incidence of the disorder rose 20-fold in the United States between 1979 and 1994, according to a study conducted by federal researchers.

But a team of scientists, led by Brown virologist Walter Atwood, has found that a handful of antipsychotic drugs can prevent brain cells from becoming infected by the JC virus. The drugs may prove to be an effective, ready-made therapy for PML prevention or treatment. Their results are published in the current issue of Science.

"This is very promising," Atwood said. "These are generic drugs we can take off the shelf that may help a lot of people."

"It is likely that there are many other drugs with none of the potential side effects of antipsychotic drugs that will also block infection," said co-author Bryan Roth, professor of biochemistry at the Case School of Medicine and director of the National Institute of Mental Health's Psychoactive Drug Screening Program.
[ ... Read the full press release ... ]

Thursday, December 02, 2004

Brain Surgery in the Early 1600s

As reported in the Boston Globe:
Skull fragment shows 400-year-old surgery in Va., researchers say
The Boston Globe
By Sonja Barisic, Associated Press
December 2, 2004

NORFOLK, Va. -- A skull fragment found in a nearly 400-year-old trash pit at Jamestown contains evidence of the earliest known surgery and possible autopsy in the English Colonies in America, researchers say.

Circular cut marks indicate someone attempted to drill two holes in the skull to relieve pressure on the brain, the researchers said. The patient, a European man, died and apparently underwent an autopsy.

Archeologists found the 4-inch-by-4-inch fragment this summer while digging in a bulwark trench on the site of James Fort. Jamestown, the first permanent English settlement in North America, was founded in 1607 as a business venture.

The skull piece was discarded with trash, such as pottery shards, from no later than about 1610, said Bly Straube, senior curator of the Association for the Preservation of Virginia Antiquities.
[ ... Read the full article ... ]

There Will Always Be Phineas

One of neuropsychology's and behavioral neuroscience's favorite historical case studies, Phineas Gage, is featured in this week's (02 December 2004) New England Journal of Medicine's "Images in Clinical Medicine" section, with two free-access .mpg videos by Peter Ratiu, M.D. and Ion-Florin Talos, M.D in their report, The Tale of Phineas Gage, Digitally Remastered.

Wednesday, December 01, 2004

Newsweek Cover Story: Memory Pharmacology

The cover story for the 06 December 2004 issue of Newsweek deals with developments in cognitive neuroscience and with drugs that may improve or enhance memory functioning:
The Quest for Memory Drugs
By Mary Carmichael
Newsweek
Dec. 6 issue - To say that Aplysia Californicus is one of nature's least glamorous beasts would be too kind. A hermaphroditic marine snail with mottled purple skin, it keeps to itself, responding to disturbances by emitting a murky fluid that stains the water around it. Its "brain," if you can call it that, is stunningly simple, with only a few thousand oversize neurons. It is not, in short, a likely candidate for glory in the animal kingdom. But a few years from now, much of the baby-boom generation may be greatly indebted to this unprepossessing little creature. Aplysia may look homely, but to scientists hoping to develop memory-enhancing medicine, it is a thing of beauty.
[ ... Read the full article ... ]