CJD mimics and chameleons

Rapidly progressive dementia mimicking Creutzfeldt-Jakob disease (CJD) is a relatively rare presentation but a rewarding one to become familiar with, as the potential diagnoses range from the universally fatal to the completely reversible. Patients require urgent decisions about assessment and investigation and have quickly evolving needs for treatments and support, through symptom management and end-of-life care in most cases. We have based this pragmatic review on the experiences of a specialist prion referral centre in the UK, which, unsurprisingly, is strongly biased towards seeing patients with CJD. Cases eventually proven not to have prion disease might be described as 'CJD-mimics'; being referred from UK neurologists, these are the most challenging cases. CJD in its classical presentation is very rarely mimicked; however, it is highly heterogeneous, and atypical forms can mimic virtually all common neurodegenerative syndromes. Warning features of a mimic include generalised seizures, hyponatraemia, fever, a facial movement disorder, a normal neurological examination and a modestly rapid presentation. Contrast-enhancing lesions or MRI signal hyperintensity outside the striatum, thalamus or cortex and a cerebrospinal fluid pleocytosis are key investigation pointers to a CJD mimic

GPAQ-R: development and psychometric properties of a version of the general practice assessment questionnaire for use for revalidation by general practitioners in the UK.

BACKGROUND: The General Practice Assessment Questionnaire (GPAQ) has been widely used to assess patient experience in general practice in the UK since 2004. In 2013, new regulations were introduced by the General Medical Council (GMC) requiring UK doctors to undertake periodic revalidation, which includes assessment of patient experience for individual doctors. We describe the development of a new version of GPAQ - GPAQ-R which addresses the GMC's requirements for revalidation as well as additional NHS requirements for surveys that GPs may need to carry out in their own practices. METHODS: Questionnaires were given out by doctors or practice staff after routine consultations in line with the guidance given by the General Medical Council for surveys to be used for revalidation. Data analysis and practice reports were provided independently. RESULTS: Data were analysed for questionnaires from 7258 patients relating to 164 GPs in 29 general practices. Levels of missing data were generally low (typically 4.5-6%). The number of returned questionnaires required to achieve reliability of 0.7 were around 35 for individual doctor communication items and 29 for a composite score based on doctor communication items. This suggests that the responses to GPAQ-R had similar reliability to the GMC's own questionnaire and we recommend 30 completed GPAQ-R questionnaires are sufficient for revalidation purposes. However, where an initial screen raises concern, the survey might be repeated with 50 completed questionnaires in order to increase reliability. CONCLUSIONS: GPAQ-R is a development of a well-established patient experience questionnaire used in general practice in the UK since 2004. This new version can be recommended for use in order to meet the UK General Medical Council's requirements for surveys to be used in revalidation of doctors. It also meets the needs of GPs to ask about patient experience relating to aspects of practice care that are not specific to individual general practitioners (e.g. receptionists, telephone access) which meet other survey requirements of the National Health Service in England. Use of GPAQ-R has the potential to reduce the number of surveys that GPs need to carry out in their practices to meet the various regulatory requirements which they face

Genome-wide association study of behavioural and psychiatric features in human prion disease.

Prion diseases are rare neurodegenerative conditions causing highly variable clinical syndromes, which often include prominent neuropsychiatric symptoms. We have recently carried out a clinical study of behavioural and psychiatric symptoms in a large prospective cohort of patients with prion disease in the United Kingdom, allowing us to operationalise specific behavioural/psychiatric phenotypes as traits in human prion disease. Here, we report exploratory genome-wide association analysis on 170 of these patients and 5200 UK controls, looking for single-nucleotide polymorphisms (SNPs) associated with three behavioural/psychiatric phenotypes in the context of prion disease. We also specifically examined a selection of candidate SNPs that have shown genome-wide association with psychiatric conditions in previously published studies, and the codon 129 polymorphism of the prion protein gene, which is known to modify various aspects of the phenotype of prion disease. No SNPs reached genome-wide significance, and there was no evidence of altered burden of known psychiatric risk alleles in relevant prion cases. SNPs showing suggestive evidence of association (P<10(-5)) included several lying near genes previously implicated in association studies of other psychiatric and neurodegenerative diseases. These include ANK3, SORL1 and a region of chromosome 6p containing several genes implicated in schizophrenia and bipolar disorder. We would encourage others to acquire phenotype data in independent cohorts of patients with prion disease as well as other neurodegenerative and neuropsychiatric conditions, to allow meta-analysis that may shed clearer light on the biological basis of these complex disease manifestations, and the diseases themselves

Imaging and CSF analyses effectively distinguish CJD from its mimics

OBJECTIVE: To review clinical and investigation findings in patients referred to a specialist prion clinic who were suspected to have sporadic Creutzfeldt-Jakob disease (sCJD) and yet were found to have an alternative final diagnosis. METHODS: Review the clinical findings and investigations in 214 patients enrolled into the UK National Prion Monitoring Cohort Study between October 2008 and November 2015 who had postmortem confirmed sCJD and compare these features with 50 patients referred over the same period who had an alternative final diagnosis (CJD mimics). RESULTS: Patients with an alternative diagnosis and those with sCJD were of similar age, sex and frequency of dementia but CJD mimics had a longer clinical history. Myoclonus, rigidity and hallucinations were more frequent in patients with sCJD but these features were not helpful in classifying individual patients. Alzheimer's disease, dementia with Lewy bodies and genetic neurodegenerative disorders were alternative diagnoses in more than half of the CJD mimic cases, and 10% had an immune-mediated encephalopathy; lymphoma, hepatic encephalopathy and progressive multifocal leukoencephalopathy were seen more than once. Diffusion-weighted MRI was the most useful readily available test to classify cases correctly (92% CJD, 2% CJD mimics). The CSF cell count, 14-3-3 protein detection and S100B were of limited value. A positive CSF RT-QuIC test, introduced during the course of the study, was found in 89% of tested CJD cases and 0% CJD mimics. CONCLUSION: The combination of diffusion-weighted MRI analysis and CSF RT-QuIC allowed a perfect classification of sCJD versus its mimics in this study

The regulated four parameter one dimensional point interaction

The general four parameter point interaction in one dimensional quantum mechanics is regulated. It allows the exact solution, but not the perturbative one. We conjecture that this is due to the interaction not being asymptotically free. We then propose a different breakup of unperturbed theory and interaction, which now is asymptotically free but leads to the same physics. The corresponding regulated potential can be solved both exactly and perturbatively, in agreement with the conjecture.Comment: 17 pages, no figures, Tex fil

Editorial

info:eu-repo/semantics/publishedVersio

Elementary Quantum Mechanics in a Space-time Lattice

Studies of quantum fields and gravity suggest the existence of a minimal length, such as Planck length \cite{Floratos,Kempf}. It is natural to ask how the existence of a minimal length may modify the results in elementary quantum mechanics (QM) problems familiar to us \cite{Gasiorowicz}. In this paper we address a simple problem from elementary non-relativistic quantum mechanics, called "particle in a box", where the usual continuum (1+1)-space-time is supplanted by a space-time lattice. Our lattice consists of a grid of $\lambda_0 \times \tau_0$ rectangles, where $\lambda_0$, the lattice parameter, is a fundamental length (say Planck length) and, we take $\tau_0$ to be equal to $\lambda_0/c$. The corresponding Schrodinger equation becomes a difference equation, the solution of which yields the $q$-eigenfunctions and $q$-eigenvalues of the energy operator as a function of $\lambda_0$. The $q$-eigenfunctions form an orthonormal set and both $q$-eigenfunctions and $q$-eigenvalues reduce to continuum solutions as $\lambda_0 \rightarrow 0 .$ The corrections to eigenvalues because of the assumed lattice is shown to be $O(\lambda_0^2).$ We then compute the uncertainties in position and momentum, $\Delta x, \Delta p$ for the box problem and study the consequent modification of Heisenberg uncertainty relation due to the assumption of space-time lattice, in contrast to modifications suggested by other investigations such as \cite{Floratos}

Berry's Phase in the Presence of a Stochastically Evolving Environment: A Geometric Mechanism for Energy-Level Broadening

The generic Berry phase scenario in which a two-level system is coupled to a second system whose dynamical coordinate is slowly-varying is generalized to allow for stochastic evolution of the slow system. The stochastic behavior is produced by coupling the slow system to a heat resevoir which is modeled by a bath of harmonic oscillators initially in equilibrium at temperature T, and whose spectral density has a bandwidth which is small compared to the energy-level spacing of the fast system. The well-known energy-level shifts produced by Berry's phase in the fast system, in conjunction with the stochastic motion of the slow system, leads to a broadening of the fast system energy-levels. In the limit of strong damping and sufficiently low temperature, we determine the degree of level-broadening analytically, and show that the slow system dynamics satisfies a Langevin equation in which Lorentz-like and electric-like forces appear as a consequence of geometrical effects. We also determine the average energy-level shift produced in the fast system by this mechanism.Comment: 29 pages, RevTex, submitted to Phys. Rev.

The Born Oppenheimer wave function near level crossing

The standard Born Oppenheimer theory does not give an accurate description of the wave function near points of level crossing. We give such a description near an isotropic conic crossing, for energies close to the crossing energy. This leads to the study of two coupled second order ordinary differential equations whose solution is described in terms of the generalized hypergeometric functions of the kind 0F3(;a,b,c;z). We find that, at low angular momenta, the mixing due to crossing is surprisingly large, scaling like \mu^(1/6), where \mu is the electron to nuclear mass ratio.Comment: 21 pages, 7 figure