Clinical manifestations of Lyme neuroborreliosis in children: a review.

Lyme neuroborreliosis (LNB) is a manifestation of Lyme disease involving the central and peripheral nervous system. It is caused by the spirochete Borrelia burgdorferi, transmitted by tick bites to a human host. Clinical signs of LNB develop after the dissemination of the pathogen to the nervous system. The infection occurs in children and adults, but the clinical manifestations differ. In adults, painful meningoradicultis is the most common manifestation of LNB, while children often present with facial nerve palsy and/or subacute meningitis. Subacute headache can be the only manifestation of LNB in children, especially during the summer months in Lyme disease-endemic regions. Non-specific symptoms, such as loss of appetite, fatigue or mood changes, may also occur, especially in young children. A high level of suspicion and early recognition of the various clinical manifestations presented by children with LNB is essential to minimize delay in diagnosis and optimize management. This review provides an overview of the spectrum of clinical manifestations, and discusses diagnosis, antibiotic treatment, and clinical outcome of LNB in children.

Clinical characteristics of Lyme neuroborreliosis in Dutch children and adults.

Lyme neuroborreliosis (LNB) is a tick-borne infection caused by Borrelia burgdorferi which can affect the nervous system in adults and children. The clinical course of LNB in adults is often different than in children. Studies comparing these differences are scarce. The aim of this study was to compare the clinical characteristics and outcome of LNB between children and adults. We performed an observational retrospective study among patients with LNB who presented at Gelre Hospital from 2007 to 2020 and had cerebrospinal fluid pleocytosis. Data were collected from electronic medical records. A total of 127 patients with LNB were identified. Included were 58 children (median age 8 years) and 69 adults (median age 56 years). The incidence of LNB was 3.2 per 100,000 inhabitants per year. The most common neurological manifestation in adults and in children was facial nerve palsy (67%). Unilateral facial nerve palsy was more prevalent in children (85%) than in adults (42%) (P < 0.001). Headache was also more prevalent in children (59%) than in adults (32%) (P = 0.003). (Poly)radiculitis was more prevalent in adults (51%) than in children (3%) (P < 0.001), encephalitis was not reported in children. In children, the time between symptom onset and diagnosis was 10 days versus 28 days in adults (P < 0.001). Complete recovery was reported significantly more often in children (83%) compared to adults (40%) (P < 0.001).    Conclusion: In a Lyme-endemic area in the Netherlands, LNB commonly presents with facial nerve palsy. Facial nerve palsy and headache are more prevalent in children, while radiculitis and encephalitis are mostly reported in adults. What is Known: • The clinical course of Lyme neuroborreliosis in adults is often different from children. . • The aim of this study was to compare the clinical characteristics and outcome of LNB between children and adults. What is New: • Lyme neuroborreliosis in the Netherlands commonly presents with facial nerve palsy. • Facial nerve palsy and headache are more prevalent in children than in adults. Radiculitis and encephalitis are mostly reported in adults.

Acute facial nerve palsy in children in a Lyme disease-endemic area in the Netherlands.

We assessed the prevalence of Lyme neuroborreliosis in children with acute facial nerve palsy in a Lyme-endemic region and patient characteristics associated with this. All children visiting one of three participating hospitals between January 2010 and December 2016 were included in the study. Of 104 children referred to the hospital with facial nerve palsy, 43% had Lyme neuroborreliosis and 57% idiopathic facial palsy. Characteristics significantly associated with Lyme neuroborreliosis were headache (55% versus 18%), meningeal irritation (21% versus 5%), presentation in summer months (69% versus 37%), and a previous tick bite (33% versus 7%).

Incidence and characteristics of Lyme neuroborreliosis in adult patients with facial palsy in an endemic area in the Netherlands.

Making a distinction between facial palsy due to Lyme neuroborreliosis (LNB) and idiopathic facial palsy (IFP) is of importance to ensure timely and adequate treatment. The study objective was to assess incidence and patient characteristics of facial palsy due to LNB. Hospital records were reviewed of adult patients with facial palsy visiting the departments of neurology and/or otorhinolaryngology of Gelre hospitals between June 2007 and December 2017. Gelre hospitals are located in an area endemic for Lyme borreliosis. Patients with LNB had pleocytosis and intrathecal antibody production or pleocytosis with positive IgG serology. Patients with IFP had negative serology. Clinical characteristics were compared between patients with LNB and patients with IFP. Five hundred and fifty-nine patients presented with facial palsy, 4.7% (26) had LNB and 39.4% (220) IFP. The incidence of facial palsy due to LNB was 0.9/100 000 inhabitants/year. Over 70% of patients with facial palsy due to LNB did not report a recent tick bite and/or erythema migrans (EM). Patients with facial palsy due to LNB presented more often in July to September (69.2% vs. 21.9%, P < 0.001), and had more often headache (42.3% vs. 15.5%, P < 0.01). To reduce the risk of underdiagnosing LNB in an endemic area, we recommend testing for LNB in patients with facial palsy in summer months especially when presenting with headache, irrespective of a recent tick bite and/or EM.

Smectic viral capsids and the aneurysm instability.

The capsids of certain Archaea-infecting viruses undergo large shape changes, while maintaining their integrity against rupture by osmotic pressure. We propose that these capsids are in a smectic liquid crystalline state, with the capsid proteins assembling along spirals. We show that smectic capsids are intrinsically stabilized against the formation of localized bulges with non-zero Gauss curvature while still allowing for large-scale cooperative shape transformation that involves global changes in the Gauss curvature.

Useful scars: Physics of the capsids of archaeal viruses.

We propose a physical model for the capsids of tailed archaeal viruses as viscoelastic membranes under tension. The fluidity is generated by thermal motion of scarlike structures that are an intrinsic feature of the ground state of large particle arrays covering surfaces with nonzero Gauss curvature. The tension is generated by a combination of the osmotic pressure of the enclosed genome and an extension force generated by filamentous structure formation that drives the formation of the tails. In continuum theory, the capsid has the shape of a surface of constant mean curvature: an unduloid. Particle arrays covering unduloids are shown to exhibit pronounced subdiffusive and diffusive single-particle transport at temperatures that are well below the melting temperature of defect-free particle arrays on a surface with zero Gauss curvature.

Equilibrium self-assembly of small RNA viruses.

We propose a description for the quasiequilibrium self-assembly of small, single-stranded (ss) RNA viruses whose capsid proteins (CPs) have flexible, positively charged, disordered tails that associate with the negatively charged RNA genome molecules. We describe the assembly of such viruses as the interplay between two coupled phase-transition-like events: the formation of the protein shell (the capsid) by CPs and the condensation of a large ss viral RNA molecule. Electrostatic repulsion between the CPs competes with attractive hydrophobic interactions and attractive interaction between neutralized RNA segments mediated by the tail groups. An assembly diagram is derived in terms of the strength of attractive interactions between CPs and between CPs and the RNA molecules. It is compared with the results of recent studies of viral assembly. We demonstrate that the conventional theory of self-assembly, which does describe the assembly of empty capsids, is in general not applicable to the self-assembly of RNA-encapsidating virions.

Statistical Physics of Viral Capsids with Broken Symmetry.

We present a model to understand quantitatively the role of symmetry breaking in assembly of macromolecular aggregates in general, and the protein shells of viruses in particular. A simple dodecahedral lattice model with a quadrupolar order parameter allows us to demonstrate how symmetry breaking may reduce the probability of assembly errors and, consequently, enhance assembly efficiency. We show that the ground state is characterized by large-scale cooperative zero-energy modes. In analogy with other models, this suggests a general physical principle: the tendency of biological molecules to generate symmetric structures competes with the tendency to break symmetry in order to achieve specific functional goals.

Elasticity theory of macromolecular aggregates.

We present a version of continuum elasticity theory applicable to aggregates of functional biomolecules at length scales comparable to that of the component molecules. Unlike classical elasticity theory, the stress and strain fields have mathematical discontinuities along the interfaces of the macromolecules, due to conformational incompatibility and large scale conformational transitions. The method is applied to the P-II to EI shape transition of the protein shell of the virus HK97. We show that protein residual stresses generated by incompatibility drive a "reverse buckling" transition from an icosahedral to a dodecahedral shape via a "critical" spherical shape, which can be identified as the P-II state.

Pulmonary consolidation and inflammation: inflammatory pseudotumour in young children.

Here we report two children with a pulmonary inflammatory pseudotumour; a rare entity in children, that often initially presents as a pneumonia, but with the possibility of serious consequences if unrecognised and untreated. One of the children presented is 6 months which is extremely young for this tumour. Difficulties in presentation, management strategies and prognosis are described. Certainly, this is a condition that should be considered even in a very young child with an inflammatory condition presenting as a solid lesion in the lung which does not resolve or even progresses.

Continuum theory of lipid bilayer electrostatics.

In order to address the concerns about the applicability of the continuum theory of lipid bilayers, we generalize it by including a film with uniaxial dielectric properties representing the polar head groups of the lipid molecules. As a function of the in-plane dielectric constant κ|| of this film, we encounter a sequence of different phases. For low values of κ||, transmembrane pores have aqueous cores, ions are repelled by the bilayer, and the ion permeability of the bilayer is independent of the ion radius as in the existing theory. For increasing κ||, a threshold is reached--of the order of the dielectric constant of water--beyond which ions are attracted to the lipid bilayer by generic polarization attraction, transmembrane pores collapse, and the ion permeability becomes sensitively dependent on the ion radius, results that are more consistent with experimental and numerical studies of the interaction of ions with neutral lipid bilayers. At even higher values of κ||, the ion/pore complexes are predicted to condense in the form of extended arrays. The generalized continuum theory can be tested quantitatively by studies of the ion permeability as a function of salt concentration and co-surfactant concentration.

Structural transitions of encapsidated polyelectrolytes.

Conformations and structural transitions of polyelectrolytes strictly confined onto a spherical 2D surface have been investigated by scaling descriptions based on physical arguments concerning polyelectrolyte adsorption onto planar surface and liquid crystals as well as by Monte Carlo simulations using a bead-spring model with short-range and electrostatic repulsions. In case of the electrostatic screened regime, a disordered-ordered (spiral) transition at increasing persistence length of the chain was found. It was predicted that the transition occurred when the persistence length is comparable with the mean spacing between adjacent strands of the ordered chain. The presence of a non-screened electrostatic repulsion led to a more complex behavior with i) a re-entrant order-disorder transition and ii) a tennis ball texture as an additional smectic/nematic structure. The various competing structures given by the theory were recovered by the Monte Carlo simulations, which also indicated that the tennis ball texture was favored over the spiral structure by the long-range interactions for semi-flexible chains.

Evaluation of two different epidural catheters in clinical practice. narrowing down the incidence of paresthesia!

Although epidural anesthesia is considered safe, several complications may occur during puncture and insertion of a catheter. Incidences of paresthesia vary between 0.2 and 56%. A prospective, open, cohort-controlled pilot study was conducted in 188 patients, ASA I-III, age 19-87 years, scheduled for elective surgery and epidural anesthesia. We evaluated a 20 G polyamide (standard) catheter and a 20 G combined polyurethane-polyamide (new) catheter. Spontaneous reactions upon catheter-insertion, paresthesia on questioning, inadvertent dural or intravascular puncture, and reasons for early catheter removal were recorded. The incidence of paresthesia reported spontaneously was 21.3% with the standard catheter and 16.7% with the new catheter. Systematically asking for paresthesia almost doubled the paraesthesia rate. Intravascular cannulation occurred in 5%. No accidental dural punctures occurred. An overall incidence of 13.3% of technical problems led to early catheter removal. The new catheter was at least equivalent to the standard regarding epidural success rate and safety : rate of paresthesia, intravascular and dural cannulation.

Continuum theory of retroviral capsids.

We present a self-assembly phase diagram for the shape of retroviral capsids, based on continuum elasticity theory. The spontaneous curvature of the capsid proteins drives a weakly first-order transition from spherical to spherocylindrical shapes. The conical capsid shape which characterizes the HIV-1 retrovirus is never stable under unconstrained energy minimization. Only under conditions of fixed volume and/or fixed spanning length can the conical shape be a minimum energy structure. Our results indicate that, unlike the capsids of small viruses, retrovirus capsids are not uniquely determined by the molecular structure of the constituent proteins but depend in an essential way on physical constraints present during assembly.

Physics of RNA and viral assembly.

The overview discusses the application of physical arguments to structure and function of single-stranded viral RNA genomes.

Structural polymorphism of DNA-dendrimer complexes.

DNA condensation in vivo relies on electrostatic complexation with small cations or large histones. We report a synchrotron x-ray study of the phase behavior of DNA complexed with synthetic cationic dendrimers of intermediate size and charge. We encounter unexpected structural transitions between columnar mesophases with in-plane square and hexagonal symmetries, as well as liquidlike disorder. The isoelectric point is a locus of structural instability. A simple model is proposed based on competing long-range electrostatic interactions and short-range entropic adhesion by counterion release.

Cavitation of Langmuir monolayers.

Cavitation in liquid expanded and liquid condensed Langmuir monolayers induced by laser heating or microbubble coalescence is studied experimentally using fluorescence and Brewster angle microscopy. The kinetics of hole closure of two-dimensional (2D) gaseous cavitation bubbles exhibits a decelerated dynamics for cavities surrounded by a liquid expanded phase and an accelerated dynamics for cavities in a liquid condensed phase. Most of the cavities in liquid condensed phases possess a nonconvex shape and do not close. The results are compared with theoretical predictions derived for 2D cavitation of liquid monolayers of different surface shear viscosities, and for solid monolayers with diffusive flux of vacancies and interstitials. While part of the theory is in qualitative agreement with the experiment, the experimentally observed hole persistence within the liquid condensed phases and the hole closure within liquid expanded phases remains to be explained. The technique of microbubble coalescence might be particularly useful for the study of the rheological properties of hexatic phases.

Raft instability of biopolymer gels.

Following recent x-ray diffraction experiments by Wong, Li, and Safinya on biopolymer gels, we apply Onsager excluded volume theory to a nematic mixture of rigid rods and strong " pi/2" cross-linkers obtaining a long-ranged, highly anisotropic depletion attraction between the linkers. This attraction leads to breakdown of the percolation theory for this class of gels, to breakdown of Onsager's second-order virial method, and to formation of heterogeneities in the form of raftlike ribbons.

Liquid crystals of polyelectrolyte networks.

The Onsager theory of nematic liquid crystals is extended to rigid polyelectrolytes cross-linked by polyvalent ions. Recent synchrotron x-ray diffraction experiments showed that dilute, birefringent networks are formed under these conditions. The application of Onsager theory to this system leads to the prediction of the existence of a range of exotic mesophases such as the "cubatic," the "tetratic," and the "trigatic." The exotic network phases appear on the border of regions of phase coexistence of network phase with isotropic material (at low polyvalent ion concentration) and with dense bundles (at high polyvalent ion concentration).