Hysterical paralysis is an uncommon type of conversion disorder. It can be difficult to diagnose. In cases in which symptoms are difficult to explain neuroanatomically or are functionally inconsistent, hysteria should enter into the differential diagnosis. We report a case of hysterical paralysis that had rapid improvement using physical therapy and antidepressant therapy.

Sleep paralysis is a relatively new term to describe what for hundreds of years many believed to be a visitation by a malevolent creature which attacked its victims as they slept. The first clinical description of sleep paralysis was published in 1664 in a Dutch physician's case histories, where it was referred to as, 'Incubus or the Night-Mare [sic]'. In 1977, it was discovered more than 100 previously healthy people from various South East Asian communities had died mysteriously in their sleep. The individuals affected were dying at a rate of 92/100,000 from Sudden Unexplained Nocturnal Death Syndrome. No underlying cause was ever found, only that subsequent studies revealed a high rate of sleep paralysis and belief in the dab tsog (nightmare spirit) amongst members of the community. The nightmare/succubus is descended from Lilith. The earliest reference to Lilith is found in the Sumerian King list of 2400 BC known as Lilitu or she-demon, she bore children from her nocturnal unions with men. In other derivations, she was Adam's first wife who rather than 'obey' became a demon that preyed on women during childbirth. In modern Middle Eastern maternity wards, some women still wear amulets for protection. Today, clinical cause of these disturbances is sleep paralysis due to the unsuitable timing of REM sleep. During the 'Nightmare' episode, the sleeper becomes partially conscious during REM cycle, leaving the individual in a state between dream and wakefulness. For some, culture and the tradition of the nightmare is explanation enough.

Honey bee viruses are associated with honey bee colony decline. Israeli acute paralysis virus (IAPV) is considered to have a strong impact on honey bee survival. Phylogenetic analysis of the viral genomes from several regions of the world showed that various IAPV lineages had substantial differences in virulence. Chronic bee paralysis virus (CBPV), another important honey bee virus, can induce two significantly different symptoms. However, the infection characteristics and pathogenesis of IAPV and CBPV have not been completely elucidated. Here, we constructed infectious clones of IAPV and CBPV using a universal vector to provide a basis for studying their replication and pathogenesis. Infectious IAPV and CBPV were rescued from molecular clones of IAPV and CBPV genomes, respectively, that induced typical paralysis symptoms. The replication levels and expression proteins of IAPV and CBPV in progeny virus production were confirmed by qPCR and Western blot. Our results will allow further dissection of the role of each gene in the context of viral infection while helping to study viral pathogenesis and develop antiviral drugs using reverse genetics systems.

No abstract available

Functional neurological disorders are characterized by neurological symptoms that have no identifiable pathology and little is known about their underlying pathophysiology.

Thyrotoxic periodic paralysis (TPP) attacks are characterized as recurrent, transient episodes of muscle weakness that range from mild weakness to complete flaccid paralysis. Episodes of weakness are accompanied by hypokalemia, which left untreated can lead to life-threatening arrhythmias (6). In this case study, we followed a patient's potassium levels analyzing how they correlate with electrocardiogram changes seen while treating his hypokalemia and ultimately his paralysis.

Brain mechanisms underlying hysterical conversion symptoms are still poorly known. Recent hypotheses suggested that activation of motor pathways might be suppressed by inhibitory signals based on particular emotional situations. To assess motor and inhibitory brain circuits during conversion paralysis, we designed a go-nogo task while a patient underwent functional magnetic resonance imaging (fMRI). Preparatory activation arose in right motor cortex despite left paralysis, indicating preserved motor intentions, but with concomitant increases in vmPFC regions that normally mediate motivational and affective processing. Failure to execute movement on go trials with the affected left hand was associated with activations in precuneus and ventrolateral frontal gyrus. However, right frontal areas normally subserving inhibition were activated by nogo trials for the right (normal) hand, but not during go trials for the left hand (affected by conversion paralysis). By contrast, a group of healthy controls who were asked to feign paralysis showed similar activation on nogo trials and left-go trials with simulated weakness, suggesting that distinct inhibitory mechanisms are implicated in simulation and conversion paralysis. In the patient, right motor cortex also showed enhanced functional connectivity with the posterior cingulate cortex, precuneus, and vmPFC. These results suggest that conversion symptoms do not act through cognitive inhibitory circuits, but involve selective activations in midline brain regions associated with self-related representations and emotion regulation.

Neural plasticity allows us to learn skills and incorporate new experiences. What happens when our lived experiences fundamentally change, such as after a severe injury? To address this question, we analyzed intracortical population activity in the posterior parietal cortex (PPC) of a tetraplegic adult as she controlled a virtual hand through a brain-computer interface (BCI). By attempting to move her fingers, she could accurately drive the corresponding virtual fingers. Neural activity during finger movements exhibited robust representational structure similar to fMRI recordings of able-bodied individuals' motor cortex, which is known to reflect able-bodied usage patterns. The finger representational structure was consistent throughout multiple sessions, even though the structure contributed to BCI decoding errors. Within individual BCI movements, the representational structure was dynamic, first resembling muscle activation patterns and then resembling the anticipated sensory consequences. Our results reveal that motor representations in PPC reflect able-bodied motor usage patterns even after paralysis, and BCIs can re-engage these stable representations to restore lost motor functions.

We aimed to determine whether jaw occlusive power decreases with the injection of neuromuscular blocking agents in masseter muscle - a method we named Sion's masseter muscle paralysis (SMP).

Chronic bee paralysis virus (CBPV) causes an infectious and contagious disease of adult honeybees. Its segmented genome is composed of two major positive single-stranded RNAs, RNA 1 (3,674 nt) and RNA 2 (2,305 nt). Three minor RNAs (about 1,000 nt each) have been described earlier but they were not detected by sequencing of CBPV genome. In this study, the results of in vivo inoculation of the two purified CBPV major RNAs are presented and demonstrate that RNA 1 and RNA 2 are infectious. Honeybees inoculated with 10(9) RNA copies per bee developed paralysis symptoms within 6 days after inoculation. The number of CBPV RNA copies increased significantly throughout the infection. Moreover, the negative strand of CBPV RNA was detected by RT-PCR, and CBPV particles were visualized by electronic microscopy in inoculated honeybees. Taken together, these results show that CBPV RNA 1 and CBPV RNA 2 segments can induce virus replication and produce CBPV virus particles. Therefore, the three minor RNAs described in early studies are not essential for virus replication. These data are crucial for the development of a reverse genetic system for CBPV.

Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base for the efficacy and effectiveness of antivenom in snakebite neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction, and the majority are either: (1) pre-synaptic neurotoxins irreversibly damaging the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the nicotinic acetylcholine receptor. Pre-clinical tests of antivenom efficacy for neurotoxicity include rodent lethality tests, which are problematic, and in vitro pharmacological tests such as nerve-muscle preparation studies, that appear to provide more clinically meaningful information. We searched MEDLINE (from 1946) and EMBASE (from 1947) until March 2017 for clinical studies. The search yielded no randomised placebo-controlled trials of antivenom for neuromuscular dysfunction. There were several randomised and non-randomised comparative trials that compared two or more doses of the same or different antivenom, and numerous cohort studies and case reports. The majority of studies available had deficiencies including poor case definition, poor study design, small sample size or no objective measures of paralysis. A number of studies demonstrated the efficacy of antivenom in human envenoming by clearing circulating venom. Studies of snakes with primarily pre-synaptic neurotoxins, such as kraits (Bungarus spp.) and taipans (Oxyuranus spp.) suggest that antivenom does not reverse established neurotoxicity, but early administration may be associated with decreased severity or prevent neurotoxicity. Small studies of snakes with mainly post-synaptic neurotoxins, including some cobra species (Naja spp.), provide preliminary evidence that neurotoxicity may be reversed with antivenom, but placebo controlled studies with objective outcome measures are required to confirm this.

A spinal cord injury interrupts pathways from the brain and brainstem that project to the lumbar spinal cord, leading to paralysis. Here we show that spatiotemporal epidural electrical stimulation (EES) of the lumbar spinal cord1-3 applied during neurorehabilitation4,5 (EESREHAB) restored walking in nine individuals with chronic spinal cord injury. This recovery involved a reduction in neuronal activity in the lumbar spinal cord of humans during walking. We hypothesized that this unexpected reduction reflects activity-dependent selection of specific neuronal subpopulations that become essential for a patient to walk after spinal cord injury. To identify these putative neurons, we modelled the technological and therapeutic features underlying EESREHAB in mice. We applied single-nucleus RNA sequencing6-9 and spatial transcriptomics10,11 to the spinal cords of these mice to chart a spatially resolved molecular atlas of recovery from paralysis. We then employed cell type12,13 and spatial prioritization to identify the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons are not required for walking before spinal cord injury, we demonstrate that they are essential for the recovery of walking with EES following spinal cord injury. Augmenting the activity of these neurons phenocopied the recovery of walking enabled by EESREHAB, whereas ablating them prevented the recovery of walking that occurs spontaneously after moderate spinal cord injury. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after paralysis. Moreover, our methodology establishes a framework for using molecular cartography to identify the neurons that produce complex behaviours.

The dicistrovirus Israeli Acute Paralysis Virus (IAPV) has been implicated in the worldwide decline of honey bees. Studies of IAPV and many other bee viruses in pure culture are restricted by available isolates and permissive cell culture. Here we show that coupling the IAPV major structural precursor protein ORF2 to its cognate 3C-like processing enzyme results in processing of the precursor to the individual structural proteins in a number of insect cell lines following expression by a recombinant baculovirus. The efficiency of expression is influenced by the level of IAPV 3C protein and moderation of its activity is required for optimal expression. The mature IAPV structural proteins assembled into empty capsids that migrated as particles on sucrose velocity gradients and showed typical dicistrovirus like morphology when examined by electron microscopy. Monoclonal antibodies raised to recombinant capsids were configured into a diagnostic test specific for the presence of IAPV. Recombinant capsids for each of the many bee viruses within the picornavirus family may provide virus specific reagents for the on-going investigation of the causes of honeybee loss.

The pollination services provided by the western honeybee (Apis mellifera) are critical for agricultural production and the diversity of wild flowering plants. However, honeybees suffer from environmental pollution, habitat loss, and pathogens, including viruses that can cause fatal diseases. Israeli acute bee paralysis virus (IAPV), from the family Dicistroviridae, has been shown to cause colony collapse disorder in the United States. Here, we present the IAPV virion structure determined to a resolution of 4.0 Å and the structure of a pentamer of capsid protein protomers at a resolution of 2.7 Å. IAPV has major capsid proteins VP1 and VP3 with noncanonical jellyroll β-barrel folds composed of only seven instead of eight β-strands, as is the rule for proteins of other viruses with the same fold. The maturation of dicistroviruses is connected to the cleavage of precursor capsid protein VP0 into subunits VP3 and VP4. We show that a putative catalytic site formed by the residues Asp-Asp-Phe of VP1 is optimally positioned to perform the cleavage. Furthermore, unlike many picornaviruses, IAPV does not contain a hydrophobic pocket in capsid protein VP1 that could be targeted by capsid-binding antiviral compounds.

Infection by a single virus can evoke diverse immune responses, resulting in different neurological outcomes, depending on the host's genetic background. To study heterogenous viral response, we use Theiler's Murine Encephalomyelitis Virus (TMEV) to model virally induced neurological phenotypes and immune responses in Collaborative Cross (CC) mice. The CC resource consists of genetically distinct and reproducible mouse lines, thus providing a population model with genetic heterogeneity similar to humans. We examined different CC strains for the effect of chronic stage TMEV-induced immune responses on neurological outcomes throughout 90 days post infection (dpi), with a particular focus on limb paralysis, by measuring serum levels of 23 different cytokines and chemokines. Each CC strain demonstrated a unique set of immune responses, regardless of presence or absence of TMEV RNA. Using stepwise regression, significant associations were identified between IL-1α, RANTES, and paralysis frequency scores. To better understand these interactions, we evaluated multiple aspects of the different CC genetic backgrounds, including haplotypes of genomic regions previously linked with TMEV pathogenesis and viral clearance or persistence, individual cytokine levels, and TMEV-relevant gene expression. These results demonstrate how loci previously associated with TMEV outcomes provide incomplete information regarding TMEV-induced paralysis in the CC strains. Overall, these findings provide insight into the complex roles of immune response in the pathogenesis of virus-associated neurological diseases influenced by host genetic background.

The situation in Europe concerning honeybees has in recent years become increasingly aggravated with steady decline in populations and/or catastrophic winter losses. This has largely been attributed to the occurrence of a variety of known and "unknown", emerging novel diseases. Previous studies have demonstrated that colonies often can harbour more than one pathogen, making identification of etiological agents with classical methods difficult. By employing an unbiased metagenomic approach, which allows the detection of both unexpected and previously unknown infectious agents, the detection of three viruses, Aphid Lethal Paralysis Virus (ALPV), Israel Acute Paralysis Virus (IAPV), and Lake Sinai Virus (LSV), in honeybees from Spain is reported in this article. The existence of a subgroup of ALPV with the ability to infect bees was only recently reported and this is the first identification of such a strain in Europe. Similarly, LSV appear to be a still unclassified group of viruses with unclear impact on colony health and these viruses have not previously been identified outside of the United States. Furthermore, our study also reveals that these bees carried a plant virus, Turnip Ringspot Virus (TuRSV), potentially serving as important vector organisms. Taken together, these results demonstrate the new possibilities opened up by high-throughput sequencing and metagenomic analysis to study emerging new diseases in domestic and wild animal populations, including honeybees.

Unilateral vocal palsy (UVFP) affects the voice and swallowing function and could be treated by various materials to achieve improved mucosal wave and better closure during phonation. Injection laryngoplasty is considered an exemplary method for these patients and could be injected as early as possible. We conducted a systematic review and meta-analysis for the subjective and objective outcomes of autologous fat injection laryngoplasty (AFIL) and assessed the effects for patients with UVFP.

Periodic paralyses (PP) are recurrent episodes of flaccid limb muscle weakness. Next to autosomal dominant forms, sporadic PP (SPP) cases are known but their genetics are unclear.

Natural killer (NK) cells are implicated as important anti-viral immune effectors in varicella zoster virus (VZV) infection. VZV can productively infect human NK cells, yet it is unknown how, or if, VZV can directly affect NK cell function. Here we demonstrate that VZV potently impairs the ability of NK cells to respond to target cell stimulation in vitro, leading to a loss of both cytotoxic and cytokine responses. Remarkably, not only were VZV infected NK cells affected, but VZV antigen negative NK cells that were exposed to virus in culture were also inhibited. This powerful impairment of function was dependent on direct contact between NK cells and VZV infected inoculum cells. Profiling of the NK cell surface receptor phenotype by multiparameter flow cytometry revealed that functional receptor expression is predominantly stable. Furthermore, inhibited NK cells were still capable of releasing cytotoxic granules when the stimulation signal bypassed receptor/ligand interactions and early signalling, suggesting that VZV paralyses NK cells from responding. Phosflow examination of key components in the degranulation signalling cascade also demonstrated perturbation following culture with VZV. In addition to inhibiting degranulation, IFN-γ and TNF production were also repressed by VZV co-culture, which was most strongly regulated in VZV infected NK cells. Interestingly, the closely related virus, herpes simplex virus type 1 (HSV-1), was also capable of efficiently infecting NK cells in a cell-associated manner, and demonstrated a similar capacity to render NK cells unresponsive to target cell stimulation-however HSV-1 differentially targeted cytokine production compared to VZV. Our findings progress a growing understanding of pathogen inhibition of NK cell function, and reveal a previously unreported strategy for VZV to manipulate the immune response.

Conversion paralysis is characterized by a loss of voluntary motor functioning without an organic cause. Despite its prevalence among neurological outpatients, little is known about the neurobiological basis of this motor dysfunction. We have examined whether the motor dysfunction in conversion paralysis can be linked to inhibition of the motor system, or rather to enhanced self-monitoring during motor behavior. We measured behavioral and cerebral responses (with fMRI) in eight conversion paralysis patients with a lateralized paresis of the arm as they were engaged in imagined actions of the affected and unaffected hand. We used a within-subjects design to compare cerebral activity during imagined movements of the affected and the unaffected hand. Motor imagery of the affected hand and the unaffected hand recruited comparable cerebral resources in the motor system, and generated equal behavioral performance. However, motor imagery of the affected limb recruited additional cerebral resources in the ventromedial prefrontal cortex and superior temporal cortex. These activation differences were caused by a failure to de-activate these regions during movement imagery of the affected hand. These findings lend support to the hypothesis that conversion paralysis is associated with heightened self-monitoring during actions with the affected arm.