Device closure for patent foramen ovale following cryptogenic stroke: a survey of current practice in the UK.

Patent foramen ovale (PFO) closure for cryptogenic stroke remains controversial due to a lack of conclusive randomised controlled data. Many experts feel PFO closure is indicated in selected cases; however, national and international guideline recommendations differ. We surveyed the UK cardiologists, stroke physicians and neurologists, seeking to determine specialist interpretation of the evidence base, and to gain an insight into the current UK practice.

Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy.

Objective: To establish the phenotypic spectrum of KIF5A mutations and to investigate whether KIF5A mutations cause axonal neuropathy associated with hereditary spastic paraplegia (HSP) or typical Charcot-Marie-Tooth disease type 2 (CMT2).

Methods: KIF5A sequencing of the motor-domain coding exons was performed in 186 patients with the clinical diagnosis of HSP and in 215 patients with typical CMT2. Another 66 patients with HSP or CMT2 with pyramidal signs were sequenced for all exons of KIF5A by targeted resequencing.

CSF neurofilaments in frontotemporal dementia compared with early onset Alzheimer's disease and controls.

Background: Frontotemporal dementia (FTD) is pathologically heterogeneous, sometimes revealing intraneuronal inclusions of neurofilaments. We therefore measured CSF neurofilament profiles in patients with FTD, patients with early onset Alzheimer's disease (EAD) and healthy control subjects to explore the discriminative potential of CSF neurofilaments compared with the existing CSF biomarkers amyloid-beta(1-42), tau and tau phosphorylated at threonine-181.

Methods: CSF levels of light chain, heavy chain and hyperphosphorylated heavy chain neurofilaments (NfL, t-NfH and P-NfH) were compared between 17 subjects with FTD, 20 with EAD and 25 cognitively healthy controls.

The natural history of Alzheimer disease: a longitudinal presymptomatic and symptomatic study of a familial cohort.

Background: Knowledge of the evolution of cognitive deficits in Alzheimer disease is important for our understanding of disease progression. Previous reports, however, have either lacked detail or have not covered the presymptomatic stages.

Objective: To delineate the onset and progression of clinical and neuropsychological abnormalities in familial Alzheimer disease.

Evidence of a founder effect in families with frontotemporal dementia that harbor the tau +16 splice mutation.

The +16 exon 10 splice mutation of the tau gene (microtubule-associated protein tau, MAPT) has been reported in numerous families with frontotemporal dementia (FTD). To date, the majority of these families are from England and Wales in the UK, although families with this mutation have been reported from Australia and the USA. Our own analysis has identified eight families with the +16 MAPT splice mutation from around the Manchester and North Wales areas of the UK.

Change in rates of cerebral atrophy over time in early-onset Alzheimer's disease: longitudinal MRI study.

The extent to which cerebral atrophy in Alzheimer's disease changes with time is unknown. We used multiple MRI scans to measure progression of cerebral atrophy in 12 patients with Alzheimer's disease who were followed up from a presymptomatic stage through to moderately severe dementia. Analysis with hierarchical regression models with quadratic terms in time provided evidence of increasing yearly percentage losses in brain volume.

Assessing the onset of structural change in familial Alzheimer's disease.

Regional and global cerebral atrophy are inevitable features of Alzheimer's disease (AD). We assessed volumes and atrophy rates of brain structures in patients with familial AD during the period that they developed symptoms. Five patients with presymptomatic AD and 20 controls had two or more annual volumetric MRI brain scans.