FRAXTAS in women inherited from mother

FRAXTAS paper in Neurology October 2010

Motor and mental dysfunction in mother–daughter transmitted FXTAS

L. Rodriguez-Revenga, BS, PhD, J. Pagonabarraga, MD, PhD, B. Gómez-Anson, MD, PhD, FRCR, O. López-Mourelo, BS, I. Madrigal, BS, PhD, M. Xunclà, BS, J. Kulisevsky, MD, PhD and M. Milà, BS, PhD From the CIBER de Enfermedades Raras (CIBERER) (L.R.-R., I.M., M.M.), Barcelona; Biochemistry and Molecular Genetics Department (L.R.-R., I.M., M.X., M.M.), Hospital Clínic, Barcelona; Neurology Service (J.P., J.K.) and Neuroradiology Unit, Radiology Department (B.G.-A.), Hospital Sant Pau, Barcelona; CIBER de Enfermedades Neurodegenerativas (CIBERNED) (J.P., B.G.-A., J.K.), Barcelona; Fundació de Recerca Hospital Sant Pau (O.L.-M.), Barcelona; PIC (O.L.-M.), IFAE, Universitat Autonoma Barcelona; Fundació Clínic per a la Recerca Biomèdica (M.X.), Barcelona; and IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (M.M.), Barcelona, Spain.
Address correspondence and reprint requests to Dr. Montserrat Milà, Biochemistry and Molecular Genetics Service, Hospital Clínic, C/Villarroel, 170, 08036 Barcelona, Spain mmila@clinic.ub.es
Objectives: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neuropsychiatric degenerative disorder that occurs predominantly in male FMR1 premutation carriers. Recently, a broader FXTAS spectrum that, besides the core features of tremor and gait ataxia, also includes neuropsychiatric symptoms and neuropathy as further clinically relevant symptoms has been described among females. Herein 2 fragile X syndrome families with a mother–daughter FXTAS transmission are described in detail in order to shed more light on the female FXTAS phenotype.
Methods: Molecular characterization included CGG repeat length, X-chromosome inactivation pattern determination, as well as FMR1 mRNA and FMRP levels quantification. Neuroradiologic examination was performed by 3-T MRI. Neuropsychological assessment included global cognitive, attention, and executive prefrontal functions, verbal fluencies, verbal memory, and visuospatial perception.
Results: Molecular, neurologic, neuropsychiatric, psychological, cognitive, and neuroradiologic features description of 2 fragile X syndrome families with a mother–daughter FXTAS transmission in which dementia is present in both mothers.
Conclusions: Although it is not yet clear to what extent FXTAS shortens lifespan, our findings show that FXTAS progresses from mild tremor and/or ataxia to disabling motor and cognitive impairment, compromising the patients' quality of life. Furthermore, our results show that FXTAS in women can also develop as a multisystem neurodegenerative disorder with central and peripheral nervous system involvement, and both motor and mental disturbances.

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Study funding: Supported by MARATO TV3 (TV06-0810), FIS 07-0770, and FIS 09-00413.

Received February 26, 2010 Accepted in final form June 28, 2010

Differences in Characteristics Among New Pediatric Neurology Patients: The Effect of a Newly Established Private Pediatric Neurology Practice

Differences in Characteristics Among New Pediatric Neurology Patients: The Effect of a Newly Established Private Pediatric Neurology Practice

Jeanne Van Cleave, MD, Brian Woodruff, MD, Gary L. Freed, MD, MPH

Received 25 July 2006; accepted 6 November 2007.

Objective

To investigate changes in volume and characteristics of new patients referred when a private pediatric neurology practice (PP) opened in 2004 in an area served primarily by an academic medical center's (AMC) pediatric neurology practice.

Methods

Retrospective analysis of medical and billing records to examine changes in volume, diagnosis, and sociodemographic factors of new patients at the AMC from July 2004 to June 2005; the PP during the same period; and the AMC during the year before.

Results

One year after the PP opened, 40% more new pediatric neurology patients were seen in this area than the year before. Compared with the AMC, PP saw a greater proportion of seizures (34% vs 26%, P < .05) and headaches (32% vs 17%, P < .001), and a lesser proportion of developmental delay/musculoskeletal disorders (12% vs 19%, P < .001) and congenital/metabolic disorders (<1%>P < .001). Fewer PP patients lived >20 miles from the practice (32% vs 64%, P < .001), and fewer had public insurance (4% vs 33%, P < .001).

Conclusions

The establishment of the PP dramatically increased the volume of new pediatric neurology patients in this area. After the PP opened, the AMC continued to care for most patients with rare diseases and fewer financial resources. Future research should examine whether the increase in volume reflects relief of pent-up demand or increased referral rates due to eased access, and should elucidate how differences in patient populations at academic and private subspecialty practices relate to access to subspecialty care and financial well-being of academic practices.

Key Words: academic medical center, pediatric neurology, private practice, referral, consultation

Timing of De Novo Mutagenesis — A Twin Study of Sodium-Channel Mutations — NEJM

Timing of De Novo Mutagenesis — A Twin Study of Sodium-Channel Mutations — NEJM

Timing of De Novo Mutagenesis — A Twin Study of Sodium-Channel Mutations

Lata Vadlamudi, M.B., B.S., Ph.D., Leanne M. Dibbens, Ph.D., Kate M. Lawrence, B.Sc., Xenia Iona, Dip.Biomed.Sci., Jacinta M. McMahon, B.Sc., Wayne Murrell, Ph.D., Alan Mackay-Sim, Ph.D., Ingrid E. Scheffer, M.B., B.S., Ph.D., and Samuel F. Berkovic, M.D.

N Engl J Med 2010; 363:1335-1340September 30, 2010

De novo mutations are a cause of sporadic disease, but little is known about the developmental timing of such mutations. We studied concordant and discordant monozygous twins with de novo mutations in the sodium channel α1 subunit gene (SCN1A) causing Dravet's syndrome, a severe epileptic encephalopathy. On the basis of our findings and the literature on mosaic cases, we conclude that de novo mutations in SCN1A may occur at any time, from the premorula stage of the embryo (causing disease in the subject) to adulthood (with mutations in the germ-line cells of parents causing disease in offspring).

Eating behaviour in narcolepsy

Abnormal eating behaviour in narcolepsy.

Sleep. 2007 Oct 1;30(10):1267-73.

Eating disorder and metabolism in narcoleptic patients.

Chabas D, Foulon C, Gonzalez J, Nasr M, Lyon-Caen O, Willer JC, Derenne JP, Arnulf I.

Fédération des maladies du système nerveux, Programme AVENIR, Inserm U546, France.

Abstract

STUDY OBJECTIVE: To evaluate eating behavior and energy balance as a cause of increased body mass index (BMI) in narcolepsy.
DESIGN: Case controlled pilot study.
SETTINGS: University hospital.
PARTICIPANTS: 13 patients with narcolepsy (7 "typical" patients, with HLA DQB1*0602 and clear cut cataplexy, with suspected hypocretin deficiency; and 6 "atypical" narcoleptics, i.e., HLA negative or without cataplexy), and 9 healthy controls matched for age, gender, and ethnicity.
INTERVENTION: Energy balance was evaluated by measuring BMI, rest energy expenditure with calorimetry, daily food and water intake, and plasma hormone levels. Eating behavior was evaluated using psychometric tests (EAT-40, EDI2, CIDI-2, MADRS).
RESULTS: Patients with narcolepsy (whether typical or not) tended to be overweight and to have a lower basal metabolism than controls. Only patients with typical narcolepsy tended to eat less than controls. Narcoleptic patients who were overweight ate half as much as others, indicating caloric restriction. Plasma glucose, cortisol, thyroid, and sex hormones levels did not differ between groups, while prolactin levels were twice as high in patients with narcolepsy as in controls. Narcoleptic patients had higher EAT-40 scores and more frequent features of bulimia nervosa (independent of depressive mood) than controls, suggesting a mild eating disorder, classified as "Eating Disorder Not Other Specified."
DISCUSSION: Both lower basal metabolism and subtle changes in eating behavior (rather than in calorie intake) could explain the positive energy balance leading to overweight in narcolepsy. Eating behavior changes may be a strategy to control weight or to avoid daytime sleepiness.

PMID: 17969460 [PubMed - indexed for MEDLINE]PMCID: PMC2266283Free PMC Article

CADASIL and skin biopsy

Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients — Brain
upper arm biopsies
granular osmophilic bodies in deep dermal arteriole basal lamina

Mixed research methods for qualitative and quantitative research

BMJ 2010; 341:c4587 doi: 10.1136/bmj.c4587 (Published 17 September 2010)

Cite this as: BMJ 2010; 341:c4587

• Research Methods & Reporting

Three techniques for integrating data in mixed methods studies

1. Alicia O’Cathain, professor1,
2. Elizabeth Murphy, professor2,
3. Jon Nicholl, professor1

+ Author Affiliations

1. ¹Medical Care Research Unit, School of Health and Related Research, University of Sheffield, Sheffield S1 4DA, UK
2. ²University of Leicester, Leicester, UK

1. Correspondence to: A O’Cathain a.ocathain@sheffield.ac.uk

• Accepted 8 June 2010

Techniques designed to combine the results of qualitative and quantitative studies can provide researchers with more knowledge than separate analysis

Health researchers are increasingly using designs that combine qualitative and quantitative methods, and this is often called mixed methods research.1 Integration—the interaction or conversation between the qualitative and quantitative components of a study—is an important aspect of mixed methods research, and, indeed, is essential to some definitions.2 Recent empirical studies of mixed methods research in health show, however, a lack of integration between components,3 4 which limits the amount of knowledge that these types of studies generate. Without integration, the knowledge yield is equivalent to that from a qualitative study and a quantitative study undertaken independently, rather than achieving a “whole greater than the sum of the parts.”5

Barriers to integration have been identified in both health and social research.6 7 One barrier is the absence of formal education in mixed methods research. Fortunately, literature is rapidly expanding to fill this educational gap, including descriptions of how to integrate data and findings from qualitative and quantitative methods.8 9 In this article we outline three techniques that may help health researchers to integrate data or findings in their mixed methods studies and show how these might enhance knowledge generated from this approach.

Triangulation protocol

Researchers will often use qualitative and quantitative methods to examine different aspects of an overall research question. For example, they might use a randomised controlled trial to assess the effectiveness of a healthcare intervention and semistructured interviews with patients and health professionals to consider the way in which the intervention was used in the real world. Alternatively, they might use a survey of service users to measure satisfaction with a service and focus groups to explore views of care in more depth. Data …

[Full text of this article]

Pregabalin is good for sleep

Check this out, pregabalin is good for sleep:

Sleep. 2005 Feb 1;28(2):187-93.

A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo.

Hindmarch I, Dawson J, Stanley N.

HPRU Medical Research Centre, University of Surrey, School of Biomedical & Molecular Sciences, Egerton Road, Guildford, UK.

Abstract

STUDY OBJECTIVES: To assess the effects of pregabalin compared with alprazolam and placebo on aspects of sleep in healthy volunteers.
DESIGN: Randomized, double-blind, placebo- and active-controlled, 3-way crossover.
SETTING: Single research center.
PARTICIPANTS AND INTERVENTIONS: Healthy adult (12 men) volunteers (N=24) received oral pregabalin 150 mg t.i.d., alprazolam 1 mg t.i.d., and placebo t.i.d. for 3 days.
MEASUREMENTS AND RESULTS: Objective sleep was measured by an 8-channel polysomnograph; subjective sleep was measured using the Leeds Sleep Evaluation Questionnaire. Compared with placebo, pregabalin significantly increased slow-wave sleep both as a proportion of the total sleep period and the duration of stage 4 sleep. Alprazolam significantly reduced slow-wave sleep. Pregabalin and alprazolam produced modest, but significant, reductions in sleep-onset latency compared with placebo. Rapid eye movement sleep latency after pregabalin was no different than placebo but was significantly shorter than that found with alprazolam. Although there were no differences between the active treatments, both pregabalin and alprazolam reduced rapid eye movement sleep as a proportion of the total sleep period compared with placebo. Pregabalin also significantly reduced the number of awakenings of more than 1 minute in duration. Leeds Sleep Evaluation Questionnaire ratings of the ease of getting to sleep and the perceived quality of sleep were significantly improved following both active treatments, and ratings of behavior following awakening were significantly impaired by both drug treatments.
CONCLUSIONS: Pregabalin appears to have an effect on sleep and sleep architecture that distinguishes it from benzodiazepines. Enhancement of slow-wave sleep is intriguing, since reductions in slow-wave sleep have frequently been reported in fibromyalgia and general anxiety disorder.

PMID: 16171242 [PubMed - indexed for MEDLINE]

The SF Community - SF-36® Health Survey Update

The SF Community - SF-36® Health Survey Update

sf36

 SF-36 Literature
 Construction of the SF-36
 Version 2.0
 Psychometric Considerations
 Translations
 Discussion

The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. It is a generic measure, as opposed to one that targets a specific age, disease, or treatment group. Accordingly, the SF-36 has proven useful in surveys of general and specific populations, comparing the relative burden of diseases, and in differentiating the health benefits produced by a wide range of different treatments. This book chapter summarizes the steps in the construction of the SF-36; how it led to the development of an even shorter (1-page, 2-minute) survey form -- the SF-12; the improvements reflected in Version 2.0 of the SF-36; psychometric studies of assumptions underlying scale construction and scoring; how they have been translated in more than 50 countries as part of the International Quality of Life Assessment (IQOLA) Project; and studies of reliability and validity.

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