Search

Prion diseases are a phenotypically diverse set of disorders characterized by protease-resistant abnormally shaped proteins known as prions. There are three main groups of prion diseases, termed sporadic (Creutzfeldt-Jakob disease [CJD], sporadic fatal insomnia, and variably protease-sensitive prionopathy), genetic (genetic CJD, fatal familial insomnia, and Gerstmann-Straussler-Scheinker syndrome), and acquired (kuru, variant CJD, and iatrogenic CJD). This article will review the pathophysiology, genetics, clinical presentations, and diagnostic challenges in patients with prion disease. Case discussions, images, and tables will be used to highlight important characteristics of prion disease and prion mimics., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Chronic meningitis is defined as cerebrospinal fluid pleocytosis that persists for at least 4 weeks without spontaneous resolution. The differential diagnosis of chronic meningitis is broad, encompassing 4 main categories, including infectious, autoimmune, neoplastic, and idiopathic. Up to one-third of cases have no discernible cause, making chronic meningitis a diagnostic dilemma for many clinicians. This article suggests a diagnostic approach to chronic meningitis using clinical history, key examination findings, selective advanced testing, and neuroimaging. Case presentations demonstrate application of a diagnostic algorithm, followed by a brief discussion on common infectious pathogens, autoimmune conditions, and neoplastic disease with selected treatment regimens., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose of Review: This article reviews the spectrum of neurologic disease associated with human herpesvirus infections., Recent Findings: As more patients are becoming therapeutically immunosuppressed, human herpesvirus infections are increasingly common. Historically, infections with human herpesviruses were described as temporal lobe encephalitis caused by herpes simplex virus type 1 or type 2. More recently, however, additional pathogens, such as varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 have been identified to cause serious neurologic infections. As literature emerges, clinical presentations of herpesvirus infections have taken on many new forms, becoming heterogeneous and involving nearly every location along the neuraxis. Advanced diagnostic methods are now available for each specific pathogen in the herpesvirus family. As data emerge on viral resistance to conventional therapies, newer antiviral medications must be considered., Summary: Infections from the herpesvirus family can have devastating neurologic outcomes without prompt and appropriate treatment. Clinical recognition of symptoms and appropriate advanced testing are necessary to correctly identify the infectious etiology. Knowledge of secondary neurologic complications of disease is equally important to prevent additional morbidity and mortality. This article discusses infections of the central and peripheral nervous systems caused by herpes simplex virus type 1 and type 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6. The pathophysiology, epidemiology, clinical presentations of disease, diagnostic investigations, imaging characteristics, and treatment for each infectious etiology are discussed in detail.

A new experimental system to measure elastic wave velocities in samples in situ under extreme conditions of pressure and temperature in a multi-anvil apparatus has been installed at Beamline 6-BM-B of the Advanced Photon Source at Argonne National Laboratory. This system allows for measurement of acoustic velocities via ultrasonic interferometry, and makes use of the synchrotron beam to measure sample densities via X-ray diffraction and sample lengths using X-radiographic imaging. This system is fully integrated into the automated software controls of the beamline and is capable of collecting robust data on elastic wave travel times in less than 1 s, which is an improvement of more than one to two orders of magnitude over existing systems. Moreover, this fast data collection time has been shown to have no effect on the obtained travel time results. This allows for more careful study of time-dependent phenomena with tighter snapshots in time of processes that would otherwise be lost or averaged out in other acoustic measurement systems.

Creutzfeldt-Jakob disease (CJD) is characterized by rapidly progressing dementia with death usually occurring within 6 months. There is no verified disease-specific pre-mortem diagnostic test besides brain biopsy. We describe a 66 y old previously high functioning male who presented with a 5 month history of rapidly progressive dementia. Neurological examination revealed a score of 19/30 on MOCA testing. An extensive workup into various causes of dementia including electroencephalography and imaging studies was unremarkable. The cerebrospinal fluid was sent to National Prion Disease Center and it revealed elevated RT-QuIC levels with negative 14-3-3 and T tau proteins. Based on literature review, our case is one of few living subjects with elevated RT-QuIC levels and negative 14-3-3 and tau proteins.

Chronic meningitis is defined as an inflammatory cerebrospinal fluid (CSF) profile that persists for at least 1 month. The presentation often includes headache, nausea, vomiting, cranial neuropathies, symptoms of elevated intracranial pressure, or focal neurologic deficits. The most common etiologies of chronic meningitis fall into 3 broad categories: infectious, autoimmune, and neoplastic. Evaluation of the patient with suspected chronic meningitis should include a detailed history and physical examination as well as repeated CSF diagnostics, serologic studies, and biopsy of the brain or other abnormal tissue (eg, lymph node or lung), when indicated. Early identification of the etiology and rapid treatment are crucial for improving morbidity and mortality, but potential infectious and neoplastic conditions should be excluded prior to empirically starting steroids or immunosuppressive medications.

Purpose of Review: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system. It has been recently associated with selective immunosuppression in patients with multiple sclerosis. This review describes the pathogenesis, clinical presentation, diagnosis, and treatment of natalizumab-associated PML., Recent Findings: Treatment of multiple sclerosis with natalizumab first involves risk stratifying patients. Clinicians can employ new tools for risk stratification including JC-virus antibody status, prior immunosuppression, and length of natalizumab treatment. These tools can help minimize the risk of developing PML. Identifying patients with natalizumab-associated PML poses a diagnostic challenge for clinicians. Unique clinical features, sensitive laboratory analyses, and advanced MRI techniques have been identified that aid in the diagnosis of natalizumab-associated PML., Summary: There continues to be significant gaps in our understanding of PML pathogenesis and its relationship with therapeutic immunosuppression. There have been advances made in our ability to treat multiple sclerosis, although these have come with the unintended risk of PML. Fortunately, natalizumab-associated PML remains a rare entity compared to multiple sclerosis-associated disability, and the risk may be mitigated with appropriate patient selection, accurate and rapid diagnosis, and aggressive treatment strategies.

Purpose of Review: This article describes the background, clinical presentation, diagnosis, and treatment of selected etiologies of subacute and chronic meningitis. Key diagnostic considerations when evaluating a patient presenting with chronic inflammation of the CNS are discussed, and several specific infectious, neoplastic, and autoimmune etiologies are reviewed in detail., Recent Findings: With recent advancement in serologic and CSF diagnostic testing, specific infectious, neoplastic, or autoimmune etiologies of chronic meningitis can be identified. Eliminating previous diagnostic uncertainty of chronic inflammation in the CNS has led to rapid and specific treatment regimens that ultimately improve patient outcomes. Recent advances in imaging have also aided clinicians in both their diagnostic approach and the detection of inflammatory complications such as hydrocephalus, hemorrhage, and ischemic stroke., Summary: Meningitis is defined as inflammation involving the meninges of the brain and spinal cord. Meningitis can be categorized as acute, subacute, or chronic based on duration of inflammation. This article focuses on the most common causes of subacute and chronic meningitis. Chronic meningitis is commonly defined as inflammation evolving during weeks to months without resolution of CSF abnormalities. Determining the time course of meningitis is important for creating a differential diagnosis. Most organisms causing acute meningitis rarely persist more than a few weeks. Although numerous etiologies of subacute and chronic meningitis have been identified, this article focuses on the most common etiologies: (1) infectious, (2) autoimmune, and (3) neoplastic.

The nervous system can be significantly affected by cancer. Neurologic symptoms are present in 30% to 50% of oncologic patients presenting to the emergency department or in neurologic consultation at teaching hospitals. Evaluation and treatment require collaborative effort between specialties. The causes of neurologic emergencies in patients with cancer are mostly related to effects of cancer, toxicities of treatments, infections, and paraneoplastic syndromes. These complications cause significant morbidity and mortality and require prompt and accurate diagnostic and treatment measures. This article reviews the common neurologic emergencies affecting patients with cancer and discusses epidemiology, clinical presentation, diagnosis, and treatment modalities., (Published by Elsevier Inc.)

Pregnancy is associated with impaired T-cell-mediated immunity putting the woman at risk for infectious diseases not typically seen in immunocompetent individuals. When maternal infection is severe, and when a primary herpesvirus infection is acquired during pregnancy, there is a risk of fetal loss, maternal death, neonatal death, or congenital abnormalities from intrauterine infection. In this review, the authors emphasize specific neurologic infectious diseases that occur in pregnancy, the safety of the antimicrobial therapy of these diseases during pregnancy, as well as the congenital and neonatal sequelae of infection., (© Thieme Medical Publishers.)

We studied the anchoring of 6CB on a series of self-assembled monolayers (SAMs) with a functional group that mimics that of the nematic liquid crystal (LC). The SAMs were first characterized by wetting, Fourier-transform infrared spectroscopy, and surface potential measurements. We found that, in two of these SAMs, the end group dipoles were oriented close to the normal of the surface and that these promoted homeotropic anchoring. In the case of the other SAM, the dipole was oriented parallel to the surface, and planar anchoring was obtained. Raman scattering by adsorbates on thin metal films is enhanced by the electromagnetic fields of surface plasmon polaritons (SPPs). Despite the inherent polarization of SPPs, there have been few reports in which SPP Raman scattering has been used to study molecular orientation. We have developed optical instrumentation to provide efficient excitation and collection of SPP Raman scattered light using attenuated total reflection geometry. The Kretschmann prism coupling configuration was used to excite SPPs on thin (500 A) gold films with adsorbed SAMs of alkanethiols in contact with thin films (50 microm) of the nematic liquid crystal 4'-hexylbiphenyl-4-carbonitrile (6CB, Merck). The anchoring and orientational wetting of the LC 6CB at the interface with omega-functionalized SAMs was studied using this arrangement. In agreement with the results of previous studies, a high-energy surface (-COOH) was found to promote planar anchoring, whereas a low-energy surface (-CF(3)) was found to induce homeotropic anchoring.

We set out to measure the standards of care in a regional cohort of women with severe hypertensive illness of pregnancy and to subsequently improve the quality of care using a series of interventions. This was a multi centre cyclical criterion audit involving 21 maternity units in the West Midlands Region. Prospective data collection involved named co-ordinators in each unit using customised proformas. Intervention comprised feedback of baseline results to each hospital, a monitoring chart and eclampsia treatment pack. The first audit period (n = 183) was for a 4-month period between 1/9/96 and 31/12/96 and the second audit period (n = 111) was during the same 4-month period 1 year later. Although compliance with the audit standards set increased in all but one standard, there is clearly a need to make further improvements in the quality of care administered.

Objective: To study the management of a series of women presenting with acute-onset hypertension in the 21 maternity units in the West Midlands region, in order to measure the standard of care and the outcomes of these patients and their babies., Design: Multicenter audit., Setting: Twenty-one Maternity Units in the West Midlands region with 85,658 births during the audit period., Methods: Prospective data collection by named coordinators (multidisciplinary) in each unit using customized proformas. The proformas were then forwarded to the Research Coordinator for input onto a database and observational analyses., Results: The total number of cases was 516. Eighty-one percent were diagnosed as having severe preeclampsia, 14% HELLP syndrome, and 5% eclampsia. Seven percent were admitted to the intensive therapy unit. Seventy percent of births were preterm, 62% of babies were low birth weight (< 2.5 kg), 57% of babies were admitted to the neonatal unit, and the perinatal mortality rate was 5%. The commonest antihypertensive agents were hydralazine and nifedipine. In terms of compliance with audit standards, 61% had both oxygen saturation and noninvasive blood pressure monitoring, 47% had good fluid balance documentation, and 79% had no fluid mismanagement. Seventy-four percent were seen by a consultant obstetrician, 62% were seen by a member of an "expert team," 83% adhered to local guidelines, and 71% of eclamptics received magnesium sulfate (MgSO4)., Conclusion: Our study shows that severe hypertensive illness of pregnancy remains an important cause of maternal mortality and perinatal mortality. This audit highlights areas in which standards of care can be improved.

Objective: The study was designed to determine whether fetal fibronectin would predict delivery before 37 weeks in women at high risk of preterm delivery., Study Methods: Forty-three women considered at risk of preterm delivery were recruited antenatally into a blind longitudinal study. Quantitative assays of fetal fibronectin were obtained from sequential high vaginal swabs taken fortnightly from 24 to 34 weeks of gestation. Fibronectin concentrations of 0.05 microgram/ml or more were considered as positive., Results: Results were calculated by swab and by subject. The sensitivity of an individual fibronectin swab in predicting preterm delivery within 14 days of testing was 71% and the specificity was 93%. The overall positive predictive value was 31% and the negative predictive value was 99%. The sensitivity of the fibronectin swab in predicting delivery before 37 weeks was 17% and the specificity was 93%. The positive predictive value was 50% and the negative predictive value was 73%. For a woman who has had a positive swab the sensitivity in predicting preterm delivery within 14 days of testing was 80% and the specificity was 83%; a woman was counted as positive only if the final swab was positive and preceded delivery by not more than 14 days. The positive predictive value was 36% and the negative predictive value was 97%. For a woman who has had a positive swab the sensitivity in predicting delivery before 37 weeks was 54%. The specificity, the positive predictive value and the negative predictive value were 85%, 64% and 79%, respectively. Women were counted as positive if any swab in the sampling sequence was positive. Fibronectin swabbing when calculated by patient did predict preterm delivery within 14 days of testing (P=0.01) and before 37 weeks (P=0.01). Analysis of the accuracy of predicting delivery from 7 to 28 days after sampling revealed that the best prediction for delivery was within the following 14 days., Conclusion: Serial fetal fibronectin assessment from 24 to 34 weeks of gestation anticipated preterm delivery within 14 days of testing and before 37 weeks for high risk asymptomatic women. Such testing should be performed every two weeks.