SummaryBackground-Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes.

SummaryBackground-Valproate is widely accepted as a drug of first choice for patients with generalised onset seizures, and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify. Lamotrigine and topiramate are also thought to possess broad spectrum activity. The SANAD study aimed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify.

Neuroferritinopathy is a progressive potentially treatable adult-onset movement disorder caused by mutations in the ferritin light chain gene (FTL1). Features overlap with common extrapyramidal disorders: idiopathic torsion dystonia, idiopathic Parkinson's disease and Huntington's disease, but the phenotype and natural history have not been defined. We studied a genetically homogeneous group of 41 subjects with the 460InsA mutation in FTL1, documenting the presentation, clinical course, biochemistry and neuroimaging. The mean age of onset was 39.4 years (SD = 13.3, range 13-63), beginning with chorea in 50%, focal lower limb dystonia in 42.5% and parkinsonism in 7.5%. The majority reported a family history of a movement disorder often misdiagnosed as Huntington's disease. The disease progressed relentlessly, becoming generalized over a 5-10 year period, eventually leading to aphonia, dysphagia and severe motor disability with subcortical/frontal cognitive dysfunction as a late feature. A characteristic action-specific facial dystonia was common (65%), and in 63% there was asymmetry throughout the disease course. Serum ferritin levels were low in the majority of males and post-menopausal females, but within normal limits for pre-menopausal females. MR brain imaging was abnormal on all affected individuals and one presymptomatic carrier. In conclusion, isolated parkinsonism is unusual in neuroferritinopathy, and unlike Huntington's disease, cognitive changes are absent or subtle in the early stages. Depressed serum ferritin is common and provides a useful screening test in routine practice, and gradient echo brain MRI will identify all symptomatic cases.

Drosophila melanogaster occurs in diverse climatic regions and shows opposing clinal changes in resistance to heat and resistance to cold along a 3000 km latitudinal transect on the eastern coast of Australia. We report here on variation at a polymorphic 8 bp-indel site in the heat shock hsr-omega gene that maps to the right arm of chromosome 3. The frequency of the genetic element marked by the L form of the gene was strongly and positively associated with latitude along this transect, and latitudinal differences in L frequency were robustly associated with latitudinal differences in maximum temperature for the hottest month. On a genetic background mixed for genes from each end of the cline a set of 10 lines was derived, five of which were fixed for the L marker, the absence of In(3R)P and 12 kb of repeats at a second polymorphic site at the 3 0 end of hsr-omega, and five that were fixed for the S marker, In(3R)P and 15 kb of hsromega repeats. For two different measures of heat tolerance S lines outperformed L lines, and for two different measures of cold tolerance L lines outperformed S lines. These data suggest that an element on the right arm of chromosome 3, possibly In(3R)P, confers heat resistance but carries the trade-off of also conferring susceptibility to cold. This element occurs at high frequency near the equator. The alternate element on the other hand, at high frequency at temperate latitudes, confers cold resistance at the cost of heat susceptibility.

Within the highly ascertained North-West England population, schwannomatosis has less than half the birth incidence and prevalence of NF2.