CSF biomarkers for dementia

Although cerebrospinal fluid (CSF) biomarker testing is incorporated into some current guidelines for the diagnosis of dementia (such as England's National Institute for Health and Care Excellence (NICE)), it is not widely accessible for most patients for whom biomarkers could potentially change management. Here we share our experience of running a clinical cognitive CSF service and discuss recent developments in laboratory testing including the use of the CSF amyloid-β 42/40 ratio and automated assay platforms. We highlight the importance of collaborative working between clinicians and laboratory staff, of preanalytical sample handling, and discuss the various factors influencing interpretation of the results in appropriate clinical contexts. We advocate for broadening access to CSF biomarkers by sharing clinical expertise, protocols and interpretation with colleagues working in psychiatry and elderly care, especially when access to CSF may be part of a pathway to disease-modifying treatments for Alzheimer's disease and other forms of dementia

Treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): an overview of systematic reviews

BackgroundChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progre ssive or relapsing and remitting disease thatusually causes weakness and sensory loss. The symptoms are due to autoimmune inflammation of peripheral nerves. CIPD affectsabout 2 to 3 per 100,000 of the population. More than half of affected people cannot walk unaided when symptoms are at their worst.CIDP usually responds to treatments th at reduce inflammation, but there is disagreement about which treatment is most effective.ObjectivesTo summarise the evidence from Cochrane systematic reviews (CSRs) and non-Cochrane systematic reviews of any treatment for CIDPand to compare the effects of treatments.MethodsWe considered all systematic reviews of randomised controlled trials (RCTs) of any treatment for any form of CIDP. We reported theirprimary outcomes, giving priority to change in disability after 12 months.Two overview authors independently identified published systematic reviews for inclusion and colle cted data. We reported the qualityof evidence using GRADE cr iter ia. Two other review authors independently checked review selection, data e xtraction and qualityassessments.On 31 October 2016, we searche d the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (intheCochrane Library), MEDLINE, Embase, and CINAHL Plus f or systematic reviews of CIDP. We suppleme nted the RCTs in theexisting CSRs by searching on the same date for RCTs of any treatment of CIDP (including treatment of fatigue or pain in CIDP), inthe Cochrane Neuromuscular Spe cialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus

Genetic and clinical characteristics of NEFL -related Charcot-Marie-Tooth disease

To analyse and describe the clinical and genetic spectrum of Charcot-Marie-Tooth disease (CMT) caused by mutations in the neurofilament light polypeptide gene ( ). Combined analysis of newly identified patients with -related CMT and all previously reported cases from the literature. Five new unrelated patients with CMT carrying the mutations P8R and N98S and the novel variant L311P were identified. Combined data from these cases and 62 kindreds from the literature revealed four common mutations (P8R, P22S, N98S and E396K) and three mutational hotspots accounting for 37 (55%) and 50 (75%) kindreds, respectively. Eight patients had de novo mutations. Loss of large-myelinated fibres was a uniform feature in a total of 21 sural nerve biopsies and 'onion bulb' formations and/or thin myelin sheaths were observed in 14 (67%) of them. The neurophysiological phenotype was broad but most patients with E90K and N98S had upper limb motor conduction velocities <38 m/s. Age of onset was ≤3 years in 25 cases. Pyramidal tract signs were described in 13 patients and 7 patients were initially diagnosed with or tested for inherited ataxia. Patients with E90K and N98S frequently presented before age 3 years and developed hearing loss or other neurological features including ataxia and/or cerebellar atrophy on brain MRI. -related CMT is clinically and genetically heterogeneous. Based on this study, however, we propose mutational hotspots and relevant clinical-genetic associations that may be helpful in the evaluation of sequence variants and the differential diagnosis with other forms of CMT