IntroductionFrontotemporal dementia (FTD) is a common cause of early-onset dementia with a significant genetic component, as underlined by the recent identification of repeat expansions in the gene C9ORF72 as a major cause of FTD and motor neuron disease. Understanding the neurobiology and clinical phenomenology of this novel mutation is currently a major research focus. However, few data are available concerning the longitudinal evolution of this genetic disease. Here we present longitudinal neuropsychological and neuroimaging data on a cohort of patients with pathological repeat expansions in C9ORF72.MethodsFollowing a review of the University College London FTD DNA database, 20 cases were retrospectively identified with a C9ORF72 expansion. Twelve cases had longitudinal neuropsychology data available and six of these cases also had longitudinal volumetric brain magnetic resonance imaging. Cortical and subcortical volumes were extracted using FreeSurfer. Rates of whole brain, hemispheric, cerebellar and ventricular change were calculated for each subject. Nonlinear fluid registration of follow-up to baseline scan was performed to visualise longitudinal intra-subject patterns of brain atrophy and ventricular expansion.ResultsPatients had low average verbal and performance IQ at baseline that became impaired (< 5th percentile) at follow-up. In particular, visual memory, naming and dominant parietal skills all showed deterioration. Mean rates of whole brain atrophy (1.4%/year) and ventricular expansion (3.2 ml/year) were substantially greater in patients with the C9ORF72 mutation than in healthy controls; atrophy was symmetrical between the cerebral hemispheres within the C9ORF72 mutation group. The thalamus and cerebellum showed significant atrophy whereas no cortical areas were preferentially affected. Longitudinal fluid imaging in individual patients demonstrated heterogeneous patterns of progressive volume loss; however, ventricular expansion and cerebellar volume loss were consistent findings.ConclusionDisease evolution in C9ORF72-associated FTD is linked neuropsychologically with increasing involvement of parietal and amnestic functions, and neuroanatomically with rather diffuse and variable cortical and central atrophy but more consistent involvement of the cerebellum and thalamus. These longitudinal profiles are consistent with disease spread within a distributed subcortical network and demonstrate the feasibility of longitudinal biomarkers for tracking the evolution of the C9ORF72 mutation phenotype.

1718 Selfish genetic elements that gain a transmission advantage through the destruction of 19 sperm have grave implications for drive male fertility. We report the first evidence for a 20 male adaptation to this negative consequence of unsuppressed drive. In the X-linked SR 21 meiotic drive system of a stalk-eyed fly, we found that drive males had greatly enlarged 22 testes and so maintained high fertility despite the destruction of half their sperm. This was 23 the case even when males were challenged with fertilising five females. Conversely, we 24 observed an overt trade-off with mating frequency due to reduced allocation of resources 25 to accessory glands. Body size and eyespan were also reduced, which are likely to impair 26 viability, pre-copulatory competition and mating frequency. Gaining an understanding of 27 the extent to which drivers promote the evolution of adaptive responses in the host is 28 essential for predictions of equilibrium frequencies in wild populations. 29

Although boys are disproportionately affected by tics in Tourette syndrome (TS), this gender bias is attenuated in adulthood and a recent study has suggested that women may experience greater functional interference from tics than men. The authors assessed the gender distribution of adults in a tertiary University-based TS clinic population and the relative influence of gender and other variables on adult tic severity (YGTSS score) and psychosocial functioning (GAF score). We also determined retrospectively the influence of gender on change in global tic severity and overall TS impairment (YGTSS) since adolescence. Females were over-represented in relation to previously published epidemiologic surveys of both TS children and adults. Female gender was associated with a greater likelihood of tic worsening as opposed to tic improvement in adulthood; a greater likelihood of expansion as opposed to contraction of motor tic distribution; and with increased current motor tic severity and tic-related impairment. However, gender explained only a small percentage of the variance of the YGTSS global severity score and none of the variance of the GAF scale score. Psychosocial functioning was influenced most strongly by tic severity but also by a variety of comorbid neuropsychiatric disorders.