NEJM Volume 358:425-428  January 24, 2008  Number 4
A Genetic Risk Factor for Periodic Limb Movements in Sleep
To the Editor: Stefansson et al. (Aug. 16 issue) report the results of a genomewide association study of the restless legs syndrome (RLS) in an Icelandic series. The analysis revealed that one single-nucleotide polymorphism (SNP) in the BTB (POZ) domain–containing 9 (BTBD9) gene was associated with RLS. Replication in smaller samples from Iceland and the United States showed that the discovery originated from a subgroup of patients with RLS who presented with periodic limb movements in sleep, a common feature of RLS. Winkelmann et al. performed a similar analysis for patients with RLS who were of European descent, with replication in samples of European or French-Canadian origin, and highlighted SNP associations in four genes in three chromosomal loci: MEIS1, BTBD9, and MAP2K5/LBXCOR1.

NEJM Volume 358:428-431  January 24, 2008  Number 4
An Appraisal of "Chronic Lyme Disease"
To the Editor: Feder et al. (Oct. 4 issue) review the great controversy surrounding "chronic Lyme disease." For most patients with this diagnosis, the authors advocate against the use of antibiotics.
But before the decision is made not to use antibiotics for patients with post–tick-bite symptoms, anaplasma, babesia, bartonella, and ehrlichia must be ruled out. These tick-borne intracellular pathogens are difficult to diagnose and can establish long-term, persistent infection. Anaplasma, babesia, and bartonella are underdiagnosed: the nonspecific symptoms of infections with these organisms tend to be ascribed to the more easily identifiable Lyme disease, which often accompanies them. Indeed, when studied prospectively, 65 of 161 patients with Lyme disease (40%) were coinfected with babesia, and 11 of 161 (7%) with anaplasma. Accurate diagnosis of these infections helps steer successful treatment: babesia and bartonella are especially difficult to eradicate. Accurate diagnosis is also important, since babesia and anaplasma can spread through blood transfusion.

BMJ  2008;336:110 (19 January), doi:10.1136/bmj.39458.446551.3A
Letters Diagnosing viral meningitis Other important diagnoses must be excluded
The crucial aspect in viral meningitis is to consider non-viral causes of aseptic meningitis and is not mentioned in the review by Logan and MacMahon.1 Of these, tuberculous meningitis and partly treated bacterial meningitis are most relevant. There are many others—for example, leptospirosis, drug related meningitis, and parameningeal brain abscess—presenting as aseptic meningitis before focal signs have developed. The findings from cerebrospinal fluid in all these conditions can be similar, even identical, to those found in viral meningitis. The authors mention various advantages in making a positive viral identification. Its real importance is in helping to exclude these non-viral illnesses. Many of them carry a serious prognosis and require immediate treatment.

BMJ  2008;336:130-133 (19 January), doi:10.1136/bmj.39412.525243.BE (published 18 December 2007)
Multifactorial assessment and targeted intervention for preventing falls and injuries among older people in community and emergency care settings: systematic review and meta-analysis
Objective To evaluate the effectiveness of multifactorial assessment and intervention programmes to prevent falls and injuries among older adults recruited to trials in primary care, community, or emergency care settings.
Design Systematic review of randomised and quasi-randomised controlled trials, and meta-analysis.
Data sources Six electronic databases (Medline, Embase, CENTRAL, CINAHL, PsycINFO, Social Science Citation Index) to 22 March 2007, reference lists of included studies, and previous reviews.
Review methods Eligible studies were randomised or quasi-randomised trials that evaluated interventions to prevent falls that were based in emergency departments, primary care, or the community that assessed multiple risk factors for falling and provided or arranged for treatments to address these risk factors.
Data extraction Outcomes were number of fallers, fall related injuries, fall rate, death, admission to hospital, contacts with health services, move to institutional care, physical activity, and quality of life. Methodological quality assessment included allocation concealment, blinding, losses and exclusions, intention to treat analysis, and reliability of outcome measurement.
Results 19 studies, of variable methodological quality, were included. The combined risk ratio for the number of fallers during follow-up among 18 trials was 0.91 (95% confidence interval 0.82 to 1.02) and for fall related injuries (eight trials) was 0.90 (0.68 to 1.20). No differences were found in admissions to hospital, emergency department attendance, death, or move to institutional care. Subgroup analyses found no evidence of different effects between interventions in different locations, populations selected for high risk of falls or unselected, and multidisciplinary teams including a doctor, but interventions that actively provide treatments may be more effective than those that provide only knowledge and referral.
Conclusions Evidence that multifactorial fall prevention programmes in primary care, community, or emergency care settings are effective in reducing the number of fallers or fall related injuries is limited. Data were insufficient to assess fall and injury rates.

BMJ  2008;336:134-138 (19 January), doi:10.1136/bmj.39408.481898.BE (published 2 January 2008)
Community occupational therapy for older patients with dementia and their care givers: cost effectiveness study
Objective To assess the cost effectiveness of community based occupational therapy compared with usual care in older patients with dementia and their care givers from a societal viewpoint.
Design Cost effectiveness study alongside a single blind randomised controlled trial.
Setting Memory clinic, day clinic of a geriatrics department, and participants’ homes.
Patients 135 patients aged 65 with mild to moderate dementia living in the community and their primary care givers.
Intervention 10 sessions of occupational therapy over five weeks, including cognitive and behavioural interventions, to train patients in the use of aids to compensate for cognitive decline and care givers in coping behaviours and supervision.
Main outcome measures Incremental cost effectiveness ratio expressed as the difference in mean total care costs per successful treatment (that is, a combined patient and care giver outcome measure of clinically relevant improvement on process, performance, and competence scales) at three months after randomisation. Bootstrap methods used to determine confidence intervals for these measures.
Results The intervention cost 1183 (£848, $1738) (95% confidence interval 1128 (£808, $1657) to 1239 (£888, $1820)) per patient and primary care giver unit at three months. Visits to general practitioners and hospital doctors cost the same in both groups but total mean costs were 1748 (£1279, $2621) lower in the intervention group, with the main cost savings in informal care. There was a significant difference in proportions of successful treatments of 36% at three months. The number needed to treat for successful treatment at three months was 2.8 (2.7 to 2.9).
Conclusions Community occupational therapy intervention for patients with dementia and their care givers is successful and cost effective, especially in terms of informal care giving.

Science 25 January 2008: Vol. 319. no. 5862, pp. 404 - 405 DOI: 10.1126/science.319.5862.404
HUMAN EVOLUTION:
Why We're Different: Probing the Gap Between Apes and Humans
Researchers at a high-level meeting probe the ancient question of what sets the human brain apart from those of other primates.

Science 25 January 2008: Vol. 319. no. 5862, pp. 406 - 408 DOI: 10.1126/science.319.5862.406
NEUROSCIENCE:
Shell Shock Revisited: Solving the Puzzle of Blast Trauma
Even at a distance, explosions may cause lasting damage to the brain. Such findings could have big implications for arming and compensating troops.

Nature 451, 465-469 (24 January 2008) | doi:10.1038/nature06469; Received 31 August 2007; Accepted 12 November 2007
Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina
Synaptic circuits in the retina transform visual input gathered by photoreceptors into messages that retinal ganglion cells (RGCs) send to the brain. Processes of retinal interneurons (amacrine and bipolar cells) form synapses on dendrites of RGCs in the inner plexiform layer (IPL). The IPL is divided into at least 10 parallel sublaminae; subsets of interneurons and RGCs arborize and form synapses in just one or a few of them. These lamina-specific circuits determine the visual features to which RGC subtypes respond. Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules—Dscam (Down's syndrome cell adhesion molecule), DscamL, Sidekick-1 and Sidekick-2 are expressed in chick by non-overlapping subsets of interneurons and RGCs that form synapses in distinct IPL sublaminae. Moreover, each protein is concentrated within the appropriate sublaminae and each mediates homophilic adhesion. Loss- and gain-of-function studies in vivo indicate that these IgSF members participate in determining the IPL sublaminae in which synaptic partners arborize and connect. Thus, vertebrate Dscams, like Drosophila Dscams, play roles in neural connectivity. Together, our results on Dscams and Sidekicks suggest the existence of an IgSF code for laminar specificity in retina and, by implication, in other parts of the central nervous system.

Nature 451, 470-474 (24 January 2008) | doi:10.1038/nature06514; Received 2 October 2007; Accepted 21 November 2007
Neurite arborization and mosaic spacing in the mouse retina require DSCAM
To establish functional circuitry, retinal neurons occupy spatial domains by arborizing their processes, which requires the self-avoidance of neurites from an individual cell, and by spacing their cell bodies, which requires positioning the soma and establishing a zone within which other cells of the same type are excluded. The mosaic patterns of distinct cell types form independently and overlap. The cues that direct these processes in the vertebrate retina are not known. Here we show that some types of retinal amacrine cells from mice with a spontaneous mutation in Down syndrome cell adhesion molecule (Dscam), a gene encoding an immunoglobulin-superfamily member adhesion molecule, have defects in the arborization of processes and in the spacing of cell bodies. In the mutant retina, cells that would normally express Dscam have hyperfasciculated processes, preventing them from creating an orderly arbor. Also, their cell bodies are randomly distributed or pulled into clumps rather than being regularly spaced mosaics. Our results indicate that mouse DSCAM mediates isoneuronal self-avoidance for arborization and heteroneuronal self-avoidance within specific cell types to prevent fasciculation and to preserve mosaic spacing. These functions are analogous to those of Drosophila DSCAM and DSCAM2. DSCAM may function similarly in other regions of the mammalian nervous system, and this role may extend to other members of the mammalian Dscam gene family.