Oculodentodigital dysplasia (ODDD) is an autosomal dominant disorder characterized by pleiotropic developmental anomalies of the limbs, teeth, face and eyes that was shown recently to be caused by mutations in the gap junction protein alpha 1 gene (GJA1), encoding connexin 43 (Cx43). In the course of performing an Nethyl-N-nitrosourea mutagenesis screen, we identified a dominant mouse mutation that exhibits many classic symptoms of ODDD, including syndactyly, enamel hypoplasia, craniofacial anomalies and cardiac dysfunction. Positional cloning revealed that these mice carry a point mutation in Gja1 leading to the substitution of a highly conserved amino acid (G60S) in Cx43. In vivo and in vitro studies revealed that the mutant Cx43 protein acts in a dominant-negative fashion to disrupt gap junction assembly and function. In addition to the classic features of ODDD, these mutant mice also showed decreased bone mass and mechanical strength, as well as altered hematopoietic stem cell and progenitor populations. Thus, these mice represent an experimental model with which to explore the clinical manifestations of ODDD and to evaluate potential intervention strategies.

Although commonly known as movement disorders, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) may present with changes in speech and language alongside or even before motor symptoms. The differential diagnosis of these two disorders can be challenging, especially in the early stages. Here we review their impact on speech and language. We discuss the neurobiological and clinical-phenomenological overlap of PSP and CBS with each other, and with other disorders including non-fluent agrammatic primary progressive aphasia and primary progressive apraxia of speech. Because language impairment is often an early and persistent problem in CBS and PSP, there is a need for improved methods for language screening in primary and secondary care, and more detailed language assessments in tertiary healthcare settings. Improved language assessment may aid differential diagnosis as well as inform clinical management decisions.

We conducted a systematic review of the literature and used meta-analytic techniques to evaluate the impact of shunt surgery on neuropsychological performance in patients with normal pressure hydrocephalus (NPH). Twenty-three studies with 1059 patients were identified for review using PubMed, Web of Science, Google scholar and manual searching. Inclusion criteria were prospective, within-subject investigations of cognitive outcome using neuropsychological assessment before and after shunt surgery in patients with NPH. There were statistically significant effects of shunt surgery on cognition (Mini-Mental State Examination; MMSE), learning and memory (Rey Auditory Verbal Learning Test; RAVLT, total and delayed subtests), executive function (backwards digit span, phonemic verbal fluency, trail making test B) and psychomotor speed (trail making test A) all in the direction of improvement following shunt surgery, but with considerable heterogeneity across all measures. A more detailed examination of the data suggested robust evidence for improved MMSE, RAVLT total, RAVLT delayed, phonemic verbal fluency and trail making test A only. Meta-regressions revealed no statistically significant effect of age, sex or follow-up interval on improvement in the MMSE. Our results suggest that shunt surgery is most sensitive for improving global cognition, learning and memory and psychomotor speed in patients with NPH.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-016-8097-0) contains supplementary material, which is available to authorized users.