Wednesday, December 28, 2005

Abstract of the Day: Patient-Reported Outcomes (PROs)

Werz MA, Schoenberg MR, Meador KJ, Loring DW, Ray PG, Kaul-Gupta R, & Ogrocki P. Subjective preference for lamotrigine or topiramate in healthy volunteers: Relationship to cognitive and behavioral functioning. Epilepsy and Behavior. 2005 Dec 21; [Epub ahead of print].

Department of Neurology, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, Cleveland, OH, USA.

OBJECTIVE: Outcomes research emphasizes patient self-assessment and preferences in optimizing treatment. We previously showed that lamotrigine produces significantly less cognitive and behavioral impairment compared with topiramate. In the current study we extend these observations to subject self-report of preference for lamotrigine or topiramate independent of potentially confounding effects of seizures or seizure control. Additionally, drug preference was related to effects of lamotrigine and topiramate on objective neuropsychological tests as well as self-perception on behavioral instruments. METHODS: Thirty-seven healthy volunteers completed a double-blind, randomized crossover design incorporating two 12-week treatment periods of lamotrigine and topiramate each titrated to a dose of 300mg/day. Evaluation of 23 objective neuropsychological and 15 subjective behavioral measures occurred at four times: pretreatment baseline, first treatment, second treatment, and posttreatment baseline. Preference for lamotrigine or topiramate was assessed, while blinding was maintained, at the final study visit when each subject was asked which drug he or she would prefer to take. RESULTS: A large majority (70%) preferred lamotrigine, 16% stated preference for topiramate, and 14% had no preference (drugs equivalent). Consistent with preference, those preferring lamotrigine performed better on 19 of 23 objective and 13 of 15 subjective behavioral measurements while on lamotrigine. Inconsistent with preference, subjects preferring topiramate performed better on 19 of 23 objective and 9 of 15 subjective behavioral measures while on lamotrigine. Topiramate preference also did not correlate with IQ, serum concentration, body mass index, age, or gender. Topiramate preference did relate to responses on the Profile of Mood States. CONCLUSION: Lamotrigine was preferred by the majority of subjects, congruent with objective neuropsychological and subjective behavioral measures. In contrast, for those stating a preference for topiramate the results on objective neuropsychological measures were impaired while fewer complaints were noted on the Profile of Mood States. This suggests that preference for topiramate may be determined by an effect on mood.

PMID: 16377253 [PubMed - as supplied by publisher]
Anthony H. Risser | |

Sunday, December 25, 2005

Abstract of the Day: Smell Identification and Anosmia Screening

Jackman AH & Doty RL. Utility of a three-item smell identification test in detecting olfactory dysfunction. Laryngoscope. 2005 Dec; 115(12): 2209-2212.
From the Smell and Taste Center, Department of Otorhinolaryngology-Head and Neck Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

OBJECTIVE:: Physicians rarely assess smell function, largely because of time considerations. Therefore, there is clinical need for very brief cranial nerve I screening tests. Although a few such tests exist, none have been adequately validated. The goal of this study was to empirically assess the utility of a three-item microencapsulated odor identification test in detecting olfactory dysfunction. SETTING:: Smell and taste center at a university medical center. METHODS:: The test was administered to 224 consecutive patients (98 men and 126 women ranging in age from 15-88 years). As part of their overall assessment, the well-validated 40-item University of Pennsylvania Smell Identification Test (UPSIT) was also administered. Sensitivity, specificity, and both negative and positive predictive values of the three-item test were established relative to UPSIT dysfunction categories. Test-retest reliability was determined in a subset of 39 patients. RESULTS:: The three-item test was abnormal in 99% (67/68) of patients with anosmia, 85% (35/41) of those with severe microsmia, 76% (31/41) of those with moderate microsmia, and 50% (17/34) of those with mild microsmia. Of the 40 normosmic patients, 62.5% (25/40) correctly identified all odors, 25% (10/40) two odors, and 12.5% (5/40) one odor. None of the normosmic patients missed all three items. Using a cut-off score of 2, the test's sensitivity and specificity were 99% and 40%, respectively, for detecting total anosmia. The corresponding negative and positive predictive values were 98% and 43%. For detecting anosmia and severe microsmia, these values were 93%, 45%, 88%, and 63%. For detecting any olfactory pathology, they were 82%, 63%, 42%, and 91%. The test-retest reliability was 0.87. CONCLUSION:: The brief three-item test used in this study was found to be highly sensitive in identifying olfactory loss in patients with chemosensory complaints, particularly those with severe dysfunction. Although only moderately specific, its high reliability and negative predictive value suggests it may be an appropriate screening test for olfactory loss.

PMID: 16369168 [PubMed - in process]
Anthony H. Risser | |

Sunday, December 18, 2005

Upcoming Event: NEUROfest, NYC, January 2006

Untitled Theater Company #61 explores the nexus of science and art in NEUROfest, the first-ever theater festival dedicated to neurological conditions.

5-29 January 2006
Theater 5
311 West 43rd Street, 5th floor

Additional info: NEUROfest homepage

A collection of theater artists from around the country will present work inspired by various neurological conditions, including: Amnesia (Korsakov's Syndrome), Aphasia, Autism, Capgras Syndrome, Creutzfeldt-Jakob Disease (CJD), Dementia, Meniere's Disease, Synesthesia, and Tourette's Syndrome.

Taken from an e-mailed release, here is the program:
Written and Directed by James Jordan
The Boondogglers
Condition dealt with: Creutzfeldt-Jakob Disease (a relative of Mad Cow)
A multimedia one man show written and performed by a neurologist about his experience with a patient with CJD, augmented with live music performance.

by Justin Warner
Directed by Ari Laura Keith
Glass House Productions
Condition dealt with: Capgras syndrome
Inspired by the rare neurological condition Capgras' Syndrome, IMPOSTORS is a quirky, funny, heartfelt exploration of the contradictions and distortions that hold all families together. After a brain injury, a son believes his parents have been replaced with exact duplicates of themselves, triggering a series of events that threatens to unravel the entire family. IMPOSTORS won the Kennedy Center-ACTF playwriting contest for the Mid-Atlantic region, and was also a finalist for the Princess Grace Award. IMPOSTORS will run simultaneously with NEUROfest at the Union Theatre in London.

Written and directed by Edward Einhorn
Untitled Theater Co. #61
Conditions dealt with: Amnesia (Korsakov's Syndrome) and Aphasia
LINGUISH posits a disease which causes aphasia, the neurological disorder that takes away one's ability to use language. Four relative strangers are among the first to be affected, and are thrown together in quarantine. As the disease affects them, they are forced to try to find new ways to communicate. In STRANGERS, a man and a woman are in what seems to be a doctor's waiting room. Is it? If so, what's wrong?

by Kirk Wood Bromley
Performed and directed by Timothy McCowen Reynolds
Inverse Theater Company
Condition dealt with: Tourette's
Syndrome is a play about a man sitting in his room attempting to muster the courage to meet his parents for dinner. We quickly discover that there are reasons for his anxiety, stemming from his submission to a "spectrum of psychological disorders" that have taken over his mind. Nothing, however, is really wrong with him.

Words by Robert Lawson, Music by Henry Akona
Directed by Henry Akona
Music Direction by Ekaterina Stanislavskaya
High Fidelity Theater
Condition dealt with: Autism
An opera featuring interlinked stories of two children, both lost in the woods. One, a 19th century tale inspired by stories of the Wild Boy of Aveyron and other children who grew up in the wild. The other, the 21st century tale of a young girl lost in the forest of mood altering medications. Tabula Rasa examines the effects of nature and nurture, and the fundamental meaning of language and human relationships.

by Jonathan Ospa, June Rachelson-Ospa, and Daniel Neiden
Music by Jody Gray, Doug Katsaros and Daniel Neiden
Directed by Daniel Neiden
Condition dealt with: Tourette's Syndrome
A musical inspired by a young boy's dreamworld where 4 aliens, Tick, Blinky, Screamer, and the guru of all Tourettians, The Big Bleeper, befriend and inspire him toward self-acceptance. The musical was co-written by June Rachelson-Ospa and her 7 year old son Jonny Ospa.

(NEUROshorts is one entire evening)

by Edward Einhorn
Directed by Barry Weil
Evolve Theater Company
Condition dealt with: Autism (Aspergers)
A fairy tale set on another planet, this is a Pinnochio story in reverse, about a child who grows up in a robot country and just wants to be a robot like everyone else.

by: Kelly R. Haydon
Directed by: Jolie Tong
Monkey Business Productions
Length: 20 minutes
Condition dealt with: Meniere's disease
As vertigo routinely attacks a former dancer stricken with Meniere's Disease, an informal conversation with his nurse turns into a revelation that challenges the idea of dependency as a passive force

by Alexandra Edwards
Directed by Julia Martin
The Transformative Theater Company
Conditions dealt with: Synesthesia, Eidetic memory
The sound of the saxophone is blue. The letter O is blue. And blue tastes good. A woman describes her world, in which every sense calls up another. When the world turns gray, she must turn to her own imaginary landscape, filled with memories, to find something delicious.

by Edward Einhorn
Directed by Ian Hill
Condition dealt with: Dementia
A found text plays about a psychologist now suffering from dementia, and her father, the discoverer of the Rh factor.

For One Night Only!
by Don Nigro
Directed by John Clancy
Theater Company: Clancy Productions
Condition dealt with: Brain tumors
A one woman show by Nancy Walsh, a portrait of madness�originally performed after the removal of a brain tumor from Nancy Walsh, allowing her to only say things she had already memorized. Done in conjunction with a seminar.
Anthony H. Risser | |

Saturday, December 17, 2005

Epilepsy: Diagnosis and Treatment Patient Care

The December issue of Postgraduate Medicine includes a series of articles on the topic of current epilepsy management. These articles can be accessed from the issue's table-of-contents page.
Anthony H. Risser | |

Wednesday, December 14, 2005

Abstract of the Day: fMRI and Auditory Attention

Nakai T, Kato C, & Matsuo K. An FMRI study to investigate auditory attention: A model of the cocktail party phenomenon. Magnetic Resonance Medical Science. 2005; 4(2): 75-82.

Functional Brain Imaging Laboratory, Department of Gerontechnology, National Center for Geriatrics and Gerontology.

In human life, discrimination of a target voice from other voices or sounds is indispensable, and inability for such discrimination results in sensory aphasia. To investigate the neuronal basis of the attentional system for human voices, we evaluated brain activity during listening comprehension tasks using functional magnetic resonance imaging (fMRI) at 3T. Diotic listening comprehension tasks, in which a narration was superimposed by another given by the same speaker (SV experiment) or by a different speaker (DV experiment), were presented to normal volunteers. The story indicated in the baseline task blocks, in which only one narration was presented, was intensively followed during the superimposed task blocks. In each experiment, 6 task blocks, 3 blocks for each condition, and 7 rest blocks were alternatively repeated, and the contrast of the superimposed condition to the baseline condition in each session was obtained. In the DV experiment, compared with the control condition, activation in Wernicke's area (BA22) was increased. In the SV experiment, activation in the frontal association cortex (BA6, BA9/ 46, BA32, BA13/47) was additionally increased. These results suggested that difficulty in phonological processing to discriminate human voices calls for further semantic, syntactic, and prosodic processing, as well as augmented selective attention.

PMID: 16340161 [PubMed - as supplied by publisher]
Anthony H. Risser | |

Saturday, December 10, 2005

p25 and Memory Functioning

From the BBC, a report about a recent research study published in the journal Neuron:
'Jekyll and Hyde' dementia clue
10 December 2005


In the study, the researchers "switched on" p25 at will in the brain's learning and memory centre, the hippocampus.

In these mice, they found that switching on p25 for only two weeks boosted learning and memory compared to normal mice.

But if the p25 was switched on for six weeks, mice displayed impaired learning and memory in tests.

Physiological studies showed that these mice showed significant brain damage and lost nerve cells in the hippocampus.

But those who had elevated p25 levels for just two weeks had no such effects.

The researchers concluded that short-term production of p25 boosts learning - but long term exposure affects the ability to form new memories.

The researchers, led by Dr Li-Huei Tsai, say the study suggested that the protein was normally beneficial, helping form memories and enable learning.

But if there was too much p25, perhaps because of other changes in the brain linked to dementias, nerve cells can die.


[ ... Read the full article ... ]
Anthony H. Risser | |

Tuesday, December 06, 2005

Abstract of the Day: Neuropsychology Assessment in Outcome from Extremely Low Birth Weight (ELBW)

Mikkola K, Ritari N, Tommiska V, Salokorpi T, Lehtonen L, Tammela O, Paakkonen L, Olsen P, Korkman M, & Fellman V. Neurodevelopmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996-1997. Pediatrics. 2005 Dec; 116(6): 1391-1400.

Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland.

OBJECTIVE: Increasing survival of extremely low birth weight (ELBW; birth weight < 1000 g) infants raises a concern regarding the risks of adverse long-term outcome such as cognitive dysfunction. Few studies have reported long-term follow-up of representative regional cohorts. The objective of this study was to assess the 5-year outcome of a prospectively followed national ELBW infant cohort. METHODS: Of all live-born ELBW infants (n = 351) who were delivered in the 2-year period 1996-1997 in Finland, 206 (59%) survived until the age of 5 years. Of these, 103 were born at < 27 gestational weeks (GW). A total of 172 children were assessed with neurocognitive tests (Wechsler Preschool and Primary Scale of Intelligence-Revised and a Developmental Neuropsychological Assessment [NEPSY]). Nine children with cognitive impairment and inability to cooperate in testing were not assessed. Motor development was assessed with a modified Touwen test. RESULTS: The rate of cognitive impairment in the ELBW survivors was 9%. The rate of cerebral palsy was 14% (19% of ELBW infants who were born at < 27 GW). The mean full-scale IQ of the assessed children was 96 +/- 19 and in children of GW < 27 was 94 +/- 19. Attention, language, sensorimotor, visuospatial, and verbal memory values of NEPSY assessment were significantly poorer compared with normal population means. Four percent needed a hearing aid, and 30% had ophthalmic findings. Of 21 children who had been treated with laser/cryo for retinopathy of prematurity, 17 (81%) had abnormal ophthalmic findings. Of the whole cohort, 41 (20%) exhibited major disabilities, 38 (19%) exhibited minor disabilities, and 124 (61%) showed development with no functional abnormalities but subtle departures from the norm. Only 53 (26%) of the total ELBW infant cohort were classified to have normal outcome excluding any abnormal ophthalmic, auditory, neurologic, or developmental findings. Being small for gestational age at birth was associated with suboptimal growth at least until age 5. CONCLUSIONS: Only one fourth of the ELBW infants were classified as normally developed at age 5. The high rate of cognitive dysfunction suggests an increased risk for learning difficulties that needs to be evaluated at a later age. Extended follow-up should be the rule in outcome studies of ELBW infant cohorts to elucidate the impact of immaturity on school achievement and social behavior later in life.

PMID: 16322163 [PubMed - in process]
Anthony H. Risser | |

Monday, December 05, 2005


From an NIH press release earlier today:
NIDCD-funded Researchers Find Missing "Piece of the Pie" in Understanding Taste

Scientists funded by the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health, are a step closer to unraveling the mystery of taste. In a study published in the December 2, 2005, issue of Science, researchers have pinpointed the chemical responsible for transmitting signals from the taste buds — small sensory bumps on the tongue, throat, and roof of the mouth — to the taste nerves leading to the brain. Today’s findings provide scientists with a more complete picture of this complicated process, helping advance the study of taste and taste disorders.

“People with taste disorders might not be able to enjoy the fun of eating and are at risk for other health problems, such as poorly balanced nutrition, so researchers are working to understand more fully how our sense of taste works,” says James F. Battey, Jr., M.D., Ph.D., director of the NIDCD. “Until now, there has always been a missing link between the detection of chemicals in the taste buds and the transmission of chemical signals from the taste nerves to the brain. Through an ingenious use of genetic engineering, these researchers have finally been able to solve the puzzle.”

Using “knockout mice,” mice that are genetically altered to be missing one or more key genes, the researchers were able to narrow the field of possible chemicals to one: adenosine 5’-triphosphate, or ATP, a high-energy molecule that is also important for helping cells in the body to function. The scientists produced mice that are missing the genes that encode two key receptors found in taste nerves — P2X2 and P2X3 — both of which bind to ATP. They found that the taste nerves of mice lacking the P2X2 and P2X3 genes showed no response to taste stimulation, although the nerves remained responsive to touch, temperature, and menthol. These results indicate that not only are P2X2 and P2X3important in transmitting taste signals, but the chemical that they bind to — ATP — is also important.
[ ... Read the full release ... ]
Anthony H. Risser | |

Saturday, December 03, 2005

Abstract of the Day: Dementia and Caregiver Quality of Life

Thomas P, Lalloue F, Preux PM, Hazif-Thomas C, Pariel S, Inscale R, Belmin J, & Clement JP. Dementia patients caregivers quality of life: The PIXEL study. International Journal of Geriatric Psychiatry. 2005 Dec 2; [Epub ahead of print]

University Department of Psychogeriatrics & Memory Clinic CH Limoges, France.

BACKGROUND: Alzheimer's disease and related syndromes have heavy social and human consequences for the patient and his family. Beyond the neuropsychiatric effects of specific therapies for dementia, one of today's challenges is the quality of life for both patients and their informal caregivers. OBJECTIVES: This survey tends to determine parameters influencing caregivers' quality of life, and its possible link with patients' quality of life. METHODS: A scale measuring caregivers' quality of life, developed from data from previous PIXEL studies was used. It is a questionnaire composed of 20 items. The scale was related to the socio-demographic data of both patients and their main caregivers, to the ADRQL scale (Alzheimer Disease Related Quality Life) of Rabins for the QoL of dementia patients, to the patients medical and therapeutic data, specially a neuropsychological inventory: Folstein's cognition test, Cornell's depression scale, the fast battery of frontal assessment, Katz's dependence index, Cummings' neuropsychiatric inventory for behavioral and psychological symptoms of dementia and to a physician evaluation of caregiver's depression. RESULTS: One hundred patients diagnosed with dementia who live at home with their principal caregivers were recruited for this survey. Patients were 80.2 +/- 6.8 years old and caregivers were 65.7 +/- 12.8 years old. The caregivers' quality of life was correlated to the quality of life of the patients they cared for, the importance of behavioral disorders, and the duration of dementia evolution. Women caregivers had a worse quality of life and were more depressive than men. DISCUSSION: Caregivers' and patients' quality of life are related and both share a community of distress. Copyright (c) 2005 John Wiley & Sons, Ltd.

PMID: 16323256 [PubMed - as supplied by publisher]
Anthony H. Risser | |

Methylphenidate Transdermal Patch (Daytrana), ADHD, & the FDA: FDA Briefing Information

Briefing Information for the FDA's psychopharmacologic drugs advisory committee meeting on Friday.
Anthony H. Risser
| |

Methylphenidate Transdermal Patch (Daytrana), ADHD, & the FDA: Thursday and Friday


From The Washington Post website:
Problem Found With Potential ADHD Patch
The Associated Press
Thursday, December 1, 2005; 3:01 PM

WASHINGTON -- A patch developed to treat attention deficit hyperactivity disorder in children received a negative review from a Food and Drug Administration scientist, who concluded the drug cannot be safely marketed.

The patch uses methylphenidate, the same drug that is in Ritalin. But FDA reviewer Dr. Robert Levin found the patch produces troubling side effects too often to be considered safe. His findings were in briefing documents released by the agency on Thursday in advance of a public meeting on the drug.

The reviewer's findings are not the final word. An independent panel of experts convened by the FDA is expected to consider on Friday whether the patch is effective and safe. The FDA has the final call on whether the patch can be made available, but the agency often follows the advice of its panels.

The patch, developed by Noven Pharmaceuticals of Miami and Shire Pharmaceuticals Group in the United Kingdom, goes on a child's hip for nine hours, according to submissions by the company. It releases into the body methylphenidate, a stimulant that calms children with ADHD. It is for children between the ages of 6 and 12.

Noven pitched the patch as a way to treat ADHD in children for whom taking pills is difficult or unpleasant. It can also be removed if it causes any side effects.

But some children who received the patch during trials reported decreased appetites, headaches, insomnia, nausea and developing tics, the FDA said. Some also had skin irritation where the patch was applied. These occurred more often than in children taking Concerta, a pill that uses methylphenidate, and those taking a placebo, the FDA said.
[ ... Read the full article ... ]


...FDA panel supports ADHD patch with limits
Fri Dec 2, 2005 4:02 PM ET
By Susan Heavey

GAITHERSBURG, Md., Dec 2 (Reuters) - An experimental patch to treat children with attention deficit hyperactivity disorder (ADHD) is safe and effective but should carry certain restrictions, a U.S. advisory panel unanimously said on Friday.

The Food and Drug Administration is considering whether to approve the patch, made by Britain's Shire Pharmaceuticals Group Plc (SHP.L...) and U.S.-based Noven Pharmaceuticals Inc (NOVN.O...). The FDA usually follows the advice of its advisers.

The panel's decision came after a key FDA staff reviewer earlier on Friday said the patch should be approved, reversing his opinion, released on Thursday, that it was too risky.

"I have reconsidered this (earlier) recommendation for a number of reasons. I think some of the safety concerns remain, but they seem to occur to a lesser degree," Robert Levin, a staff reviewer in the FDA's Division of Psychiatry Products, told panelists.
[ ... Read the full article ... ]
Anthony H. Risser
| |

Friday, December 02, 2005

Malnutrition and the Brain

From the December issue of The APA Monitor:
Feed the birds
Songbird study offers new insights into how malnutrition impairs development and cognition
By Rachel Adelson
The APA Monitor
December 2005
Print version: page 16

Slim postpartum pickings for young birds may stunt their brain growth and impede their ability to later remember where they store food. In fact, early deprivation may send adult birds into a downward spiral and thwart their survival, according to new research by Vladimir Pravosudov, PhD, of the University of Nevada, Reno, and Pierre Lavenex, PhD, and Alicja Omanska, PhD, of the University of California, Davis.

They studied the impact of early malnutrition on the western scrub-jay, a long-tailed, blue-feathered songbird. They underfed scrub-jay chicks. Then a year later, when these scrawny chicks grew up, they were worse off as adults than birds who ate better when young–even though the experimental group had caught up by then in weight. The experimental birds had smaller hippocampi with fewer neurons than the control birds and performed worse on spatial-memory tasks that required them to recover seeds they had cached away.
[ ... Read the full article ... ]
Anthony H. Risser | |