Nervous System Impairment Research Articles

The role of myocardial innervation imaging in different clinical scenarios: an expert document of the European Association of Cardiovascular Imaging and Cardiovascular Committee of the European Association of Nuclear Medicine.

Cardiac sympathetic activity plays a key role in supporting cardiac function in both health and disease conditions, and nuclear cardiac imaging has always represented the only way for the non-invasive evaluation of the functional integrity of cardiac sympathetic terminals, mainly through the use of radiopharmaceuticals that are analogues of norepinephrine and, in particular, with the use of 123I-mIBG imaging. This technique demonstrates the presence of cardiac sympathetic dysfunction in different cardiac pathologies, linking the severity of sympathetic nervous system impairment to adverse patient's prognosis. This article will outline the state-of-the-art of cardiac 123I-mIBG imaging and define the value and clinical applications in the different fields of cardiovascular diseases.

Müller glia-myeloid cell crosstalk accelerates optic nerve regeneration in the adult zebrafish.

Neurodegenerative disorders, characterized by progressive neuronal loss, eventually lead to functional impairment in the adult mammalian central nervous system (CNS). Importantly, these deteriorations are irreversible, due to the very limited regenerative potential of these CNS neurons. Stimulating and redirecting neuroinflammation was recently put forward as an important approach to induce axonal regeneration, but it remains elusive how inflammatory processes and CNS repair are intertwined. To gain more insight into these interactions, we investigated how immunomodulation affects the regenerative outcome after optic nerve crush (ONC) in the spontaneously regenerating zebrafish. First, inducing intraocular inflammation using zymosan resulted in an acute inflammatory response, characterized by an increased infiltration and proliferation of innate blood-borne immune cells, reactivation of Müller glia, and altered retinal cytokine expression. Strikingly, inflammatory stimulation also accelerated axonal regrowth after optic nerve injury. Second, we demonstrated that acute depletion of both microglia and macrophages in the retina, using pharmacological treatments with both the CSF1R inhibitor PLX3397 and clodronate liposomes, compromised optic nerve regeneration. Moreover, we observed that csf1ra/b double mutant fish, lacking microglia in both retina and brain, displayed accelerated RGC axonal regrowth after ONC, which was accompanied with unusual Müller glia proliferative gliosis. Altogether, our results highlight the importance of altered glial cell interactions in the axonal regeneration process after ONC in adult zebrafish. Unraveling the relative contribution of the different cell types, as well as the signaling pathways involved, may pinpoint new targets to stimulate repair in the vertebrate CNS.

LESCH-NYHAN SYNDROME – late diagnosis of rare disease: clinical case

Background. Lesch-Nyhan syndrome is inherent X-linked recessive genetic disorder with decreased activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT). The disease is characterized by presence of the classical triad: hyperuricemia, neurological and behavioral changes. In the article we present a clinical case of Lesch-Nyhan syndrome first diagnosed only at 16 years old despite the fact that the clinical clues were already found at the patient`s early age. Case presentation. An 18-year-old Caucasian man was admitted to the rheumatology department because of gouty arthritis. In neonatal period he was diagnosed with mild intrauterine growth restriction by hypoplastic type. Uric acid crystals were found in our patient`s urine at 6-month-old. In the first year of life, delayed motor development was noted together with permanent neurological changes which were referred to rickets. During school years, severe dysgraphia, dyslexia, dysarthria, logoneurosis warranted observation by a speech therapist. At his 12 he had been diagnosed with nephrocalcinosis, at 14 – with chronic kidney disease and symptomatic arterial hypertension. The family history was remarkable for gout in grandmother and great-grandmother, chronic pyelonephritis – in mother, urate nephropathy – in both brothers. In physical examination hyperemia and edema of the left first metatarsophalangeal joint, left ankle defiguration, funnel chest, gynecomastia, tophi on the ears were noted. On examination, some neurological disorders and mild cognitive impairment were found. In investigations hyperuricemia, arthritis of the first metatarsophalangeal joint, diffuse changes in the renal parenchyma with impaired renal excretory function were detected. Despite the clues in patient`s anamnesis, objective examination and additional investigation, as well as the presence of a family anamnesis suggesting the hereditary nature of hyperuricemia, the diagnosis of HGPRT deficiency was not made until the age of 16 years. Conclusion. The presence of Lesch-Nyhan syndrome can be assumed with the progression of muscle tone impairment and movement disorders in a child after the first six months of life in combination with high plasma uric acid concentration and its increased urinary excretion. Difficulties in the syndrome diagnosis are associated not only with a rare occurrence, but with a slight or moderate degree of central nervous system impairment that is often related by doctors to rickets or delivery trauma, as well as low accessibility of molecular genetic testing.

Complementarity of pain assessment instruments in children with central nervous system impairment

ABSTRACT Objective: To evaluate the complementarity of the revised Face, Legs, Activity, Cry, Consolability scale and of the Inventory of Pain Behavior in Neurological Disability for the assessment of pain in children with severe neurological impairment. Method: Cross-sectional study conducted in pediatric units of a university hospital in the southern region of Brazil. The sample consisted of 26 children with severe neurological impairment, hospitalized from January to August 2019, and their caregivers. The data were analyzed by descriptive statistics; Kappa Coefficient, Fisher’s Exact Test and Spearman’s Coefficient were used (p≤0,05). Results: Most children primary diagnosis was cerebral palsy (80.8%). Pain was present in 50.0% of children with the application of the scale and in 34.6% with that of the inventory. Considering the two instruments, there was good agreement (84.6%) between respondents (k=0.692; 95% CI 0.437-0.967; p=0.000). Conclusion: The instruments can be used complementarily to assess pain in children with this profile.

Tuberculosis Presenting as Thrombotic Thrombocytopenic Purpura

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure, and central nervous system impairment. Clinical Description: Although most cases of TTP are idiopathic, there are some case reports describing its association with certain infections. We report a rare case of TTP associated with tuberculosis which was confirmed by ADAMTS13 levels. Management: This child was managed with high-dose plasma infusion. Conclusion: To the best of our knowledge, this is the first case in a pediatric patient with this association and treated successfully by high-dose plasma infusion.

The Importance of Non-Coding RNAs in Neurodegenerative Processes of Diabetes-Related Molecular Pathways.

Diabetes mellitus (DM) is a complex condition and serious health problem, with growing occurrence of DM-associated complications occurring globally. Persistent hyperglycemia is confirmed as promoting neurovascular dysfunction leading to irreversible endothelial cell dysfunction, increased neuronal cell apoptosis, oxidative stress and inflammation. These collaboratively and individually result in micro- and macroangiopathy as well as neuropathy demonstrated by progressive neuronal loss. Recently, major efforts have been pursued to select not only useful diagnostic and prognostic biomarkers, but also novel therapeutic approaches. Both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) belong to a class of non-coding RNAs identified in most of the body fluids i.e., peripheral blood, cerebrospinal fluid, brain tissue and neurons. Numerous miRNAs, lncRNAs and their target genes are able to modulate signaling pathways known to play a role in the pathophysiology of progressive neuronal dysfunction. Therefore, they pose as promising biomarkers and treatment for the vast majority of neurodegenerative disorders. This review provides an overall assessment of both miRNAs’ and lncRNAs’ utility in decelerating progressive nervous system impairment, including neurodegeneration in diabetic pathways.

Occupational exposure as a risk factor for cognitive impairment in Vietnamese nail salon workers

AbstractBackgroundNail salon technicians are continuously exposed to neurotoxic and carcinogenic properties in nail products that may put them at risk for central nervous system impairments linked to Alzheimer’s disease. However, there are very few studies of the nail‐care workplace, and even fewer focus on Vietnamese female nail technicians, who make up the overwhelming part of the workforce. This study provides preliminary data on clinical assessments that will inform the cognitive functioning of a vulnerable population.MethodSample includes 300 Vietnamese females aged 50 or above in Northern California. The nail‐technician group (n=155) self‐identified as a current or former full or part‐time nail technician. The non‐nail group (n=145) are those who have never worked in the cosmetic industry, including nail or hair salons, but were an approximate match with the nail technicians on demographics and acculturation variables. Participants completed the Montreal Cognitive Assessment (MoCA), the Center for Epidemiologic Studies Depression Scale (CES‐D), and a self‐reported bilingual survey regarding their occupational exposure and demographics.ResultThe average MoCA score was 18.8 (SD ±4.50) for non‐nail technicians, which is significantly higher than 17.60 (SD ±4.30) for nail technicians (p = 0.017). However, there was no significant difference between the two groups on the average CES‐D score (p = 0.22). Based on results of multiple linear regression, with an increase of 100 in exposure index (i.e., years working in current nail salon x hours worked per week), the MoCA score is expected to decrease by 0.29 (95% CI: 0.05, 0.53, p = 0.017).ConclusionAfter adjusting for potential confounders, Vietnamese nail technicians were found to have lower cognitive functioning that those without occupational exposure to nail salon work. The results of this study suggest the need for future longitudinal research to better elucidate the processes underlying this association.

Age-Related Deficits in Binocular Vision Are Associated With Poorer Inhibitory Control in Healthy Older Adults.

A robust association between reduced visual acuity and cognitive function in older adults has been revealed in large population studies. The aim of this work was to assess the relation between stereoacuity, a key aspect of binocular vision, and inhibitory control, an important component of executive functions. Inhibition was tested using the antisaccade task in older adults with normal or reduced stereopsis (study 1), and in young adults with transiently reduced stereopsis (study 2). Older adults with reduced stereopsis made significantly more errors on the antisaccade task in comparison to those with normal stereopsis. Specifically, there was a significant correlation between stereoacuity and antisaccade errors (r = 0.27, p = 0.019). In contrast, there were no significant differences in antisaccade errors between the normal and reduced stereopsis conditions in the young group. Altogether, results suggest that the association between poorer stereopsis and lower inhibitory control in older adults might arise due to central nervous system impairment that affects the processing of binocular disparity and antisaccades. These results add to a growing body of literature, which highlights the interdependence of sensory and cognitive decline in older adults.

Sphingosine-1-Phosphate Receptor Modulators and Oligodendroglial Cells: Beyond Immunomodulation.

Multiple sclerosis (MS) is an autoimmune inflammatory disease characterized by demyelination, axonal loss, and synaptic impairment in the central nervous system (CNS). The available therapies aim to reduce the severity of the pathology during the early inflammatory stages, but they are not effective in the chronic stage of the disease. In this phase, failure in endogenous remyelination is associated with the impairment of oligodendrocytes progenitor cells (OPCs) to migrate and differentiate into mature myelinating oligodendrocytes. Therefore, stimulating differentiation of OPCs into myelinating oligodendrocytes has become one of the main goals of new therapeutic approaches for MS. Different disease-modifying therapies targeting sphingosine-1-phosphate receptors (S1PRs) have been approved or are being developed to treat MS. Besides their immunomodulatory effects, growing evidence suggests that targeting S1PRs modulates mechanisms beyond immunomodulation, such as remyelination. In this context, this review focuses on the current understanding of S1PR modulators and their direct effect on OPCs and oligodendrocytes.

Biallelic loss-of-function variants in NEMF cause central nervous system impairment and axonal polyneuropathy.

We aimed to detect the causative gene in five unrelated families with recessive inheritance pattern neurological disorders involving the central nervous system, and the potential function of the NEMF gene in the central nervous system. Exome sequencing (ES) was applied to all families and linkage analysis was performed on family 1. A minigene assay was used to validate the splicing effect of the relevant discovered variants. Immunofluorescence (IF) experiment was performed to investigate the role of the causative gene in neuron development. The large consanguineous family confirms the phenotype-causative relationship with homozygous frameshift variant (NM_004713.6:c.2618del) as revealed by ES. Linkage analysis of the family showed a significant single-point LOD of 4.5 locus. Through collaboration in GeneMatcher, four additional unrelated families' likely pathogenic NEMF variants for a spectrum of central neurological disorders, two homozygous splice-site variants (NM_004713.6:c.574+1G>T and NM_004713.6:c.807-2A>C) and a homozygous frameshift variant (NM_004713.6: c.1234_1235insC) were subsequently identified and segregated with all affected individuals. We further revealed that knockdown (KD) of Nemf leads to impairment of axonal outgrowth and synapse development in cultured mouse primary cortical neurons. Our study demonstrates that disease-causing biallelic NEMF variants result in central nervous system impairment and other variable features. NEMF is an important player in mammalian neuron development.

Speech treatment in nemaline myopathy: A single-subject experimental study

PurposeThe objective of this work was to verify the efficacy of a treatment based on myofunctional therapy techniques which aimed to improve the tongue strength, precision, and speed of a ten-year-old girl with nemaline myopathy (NM) and the repercussions of this therapy on her speech intelligibility. NM is a rare congenital muscle disorder that causes extreme muscle weakness, especially in the face and neck, as well as severe dysarthria and dysphagia, although this does not affect the nervous system or cognitive development. MethodThis was a single-subject experimental study which used an interrupted pre- and post-treatment time-series design, and which applied autoregressive integrated moving-average predictive models and Holt exponential smoothing. During the treatment phases, the participant’s tongue strength and the rate of speech diadochokinesia and voluntary lingual movements were estimated and the repercussions of the intervention in terms of speech intelligibility were ascertained via an experiment with ‘naïve’ judges. ResultsThe treatment produced a sustained and significant increase in the maximum strength of the patient’s tongue, which increased from an initial 4 kPa to 11 kPa at the end of the treatment phase. However, this was far from the average 58 kPa for age- and sex-matched normative data. There were no significant changes either in the rates of voluntary lingual mobility or speech diadochokinesia. Speech intelligibility, as assessed by naïve judges, improved from 40 % in the pre-treatment phase to 67 % in the post-treatment phase. ConclusionsNM and other rare primary muscle disorders allow us to estimate the effects of severe muscle weakness in people with dysarthria without cognitive impairment or alterations in central nervous system, peripheral nervous system or in gap junction. In this case, the treatment did not increase the patient’s lingual and articulatory movement speed but did increase her tongue strength from 5 % to 10 % of the levels otherwise expected for her age and significantly improved the intelligibility of her speech and communication.

Exosomes released from Shiga toxin 2a-treated human macrophages modulate inflammatory responses and induce cell death in toxin receptor expressing human cells.

Shiga toxins (Stxs) produced by Stx-producing Escherichia coli are the primarily virulence factors of hemolytic uremic syndrome and central nervous system (CNS) impairment. Although the precise mechanisms of toxin dissemination remain unclear, Stxs bind to extracellular vesicles (EVs). Exosomes, a subset of EVs, may play a key role in Stx-mediated renal injury. To test this hypothesis, we isolated exosomes from monocyte-derived macrophages in the presence of Stx2a or Stx2 toxoids. Macrophage-like differentiated THP-1 cells treated with Stxs secreted Stx-associated exosomes (Stx-Exo) of 90-130 nm in diameter, which induced cytotoxicity in recipient cells in a toxin receptor globotriaosylceramide (Gb3 )-dependent manner. Stx2-Exo engulfed by Gb3 -positive cells were translocated to the endoplasmic reticulum in the human proximal tubule epithelial cell line HK-2. Stx2-Exo contained pro-inflammatory cytokine mRNAs and proteins and induced more severe inflammation than purified Stx2a accompanied by greater death of target cells such as human renal or retinal pigment epithelial cells. Blockade of exosome biogenesis using the pharmacological inhibitor GW4869 reduced Stx2-Exo-mediated human renal cell death. Stx2-Exo isolated from human primary monocyte-derived macrophages activated caspase 3/7 and resulted in significant cell death in primary human renal cortical epithelial cells. Based on these results, we speculate that Stx-containing exosomes derived from macrophages may exacerbate cytotoxicity and inflammation and trigger cell death in toxin-sensitive cells. Therapeutic interventions targeting Stx-containing exosomes may prevent or ameliorate Stx-mediated acute vascular dysfunction.

Cellular and molecular mechanisms of DEET toxicity and disease-carrying insect vectors: a review

Several insects such as mosquitoes, flies, ticks, fleas, lice, and mites are known to serve as vectors for a vast number of pathogens. Many such vectors are hematophagous, and therefore introduce pathogens directly into the host's bloodstream. Importantly, the capacity of these vectors to spread disease can lead to serious global health crises. Furthermore, crop damage can be exacerbated by pathogen infection and increased insect foraging due to recent global warming. Our study categorized insect-associated damage into three groups: animal infection, plant infection, and direct crop damage due to insect foraging. To manage these problems, insect repellents and pesticides have been developed, among which DEET is the most broadly used and studied pest control agent. This review discusses the mode of action and possible mechanisms of DEET action, including olfactory and gustatory mechanisms and central nervous system impairment. To protect humans from malaria, yellow fever, dengue fever, zika, and filariasis, as well as to reduce economic losses associated with crop damage, considerably more efforts are needed to characterize the interactions between insects and insect repellents/pesticides to develop more potent pest control agents.

ApoE Lipidation as a Therapeutic Target in Alzheimer's Disease.

Apolipoprotein E (APOE) is the major cholesterol carrier in the brain, affecting various normal cellular processes including neuronal growth, repair and remodeling of membranes, synaptogenesis, clearance and degradation of amyloid β (Aβ) and neuroinflammation. In humans, the APOE gene has three common allelic variants, termed E2, E3, and E4. APOE4 is considered the strongest genetic risk factor for Alzheimer’s disease (AD), whereas APOE2 is neuroprotective. To perform its normal functions, apoE must be secreted and properly lipidated, a process influenced by the structural differences associated with apoE isoforms. Here we highlight the importance of lipidated apoE as well as the APOE-lipidation targeted therapeutic approaches that have the potential to correct or prevent neurodegeneration. Many of these approaches have been validated using diverse cellular and animal models. Overall, there is great potential to improve the lipidated state of apoE with the goal of ameliorating APOE-associated central nervous system impairments.

A-088 Case Report: Neuropsychological Assessment of Giant Axonal Neuropathy in Adulthood

Abstract Objective Giant axonal neuropathy (GAN) is a progressive condition marked by abnormally large/dysfunctional axons. Childhood neurological symptoms (e.g., ataxia, loss of sensation, strength, and reflexes in limbs, and visual and hearing problems) eventually lead to central nervous system impairment (e.g., seizures, paralysis, and cognitive decline). The scant literature on cognition in GAN is mixed, with findings from no impairment all the way to dementia. We present a case of an adult GAN patient with milder symptoms. Method A 55-year-old Hispanic male with 13 years of education was referred from outpatient neurology for neuropsychological evaluation in a county hospital setting. He was symptomatic in childhood, but was not diagnosed with GAN until 2018. A comprehensive neuropsychological evaluation was conducted. His presentation was notable for anxious and restricted affect, rapid speech, and intense gaze. He appeared immature and at times guarded about his symptoms and history. Results Cognitive test results were valid and indicated normal-range IQ and generally intact cognitive abilities with mixed performances (and mild deficits) in visual memory and executive functioning. The MMPI-2-RF was invalid due to elevations on multiple validity scales, possibly due to limited insight and/or impression management (L-r highest). Conclusions The results add to the limited literature on cognition in GAN by describing a milder case. Our patient demonstrated some mixed cognitive difficulties as well as idiosyncrasies in personality that could reflect immaturity and/or reduced insight. In addition to further exploring its cognitive effects, future research into GAN should include the evaluation of personality and insight/metacognition in patients with milder symptoms.

Brainstem auditory evoked potentials in patients with primary Sj\xf6gren\u2019s syndrome without central nervous system involvement

ObjectivesPrimary Sjögren’s syndrome (pSS) is an autoimmune, multisystem exocrinopathy characterized by dysfunction of the exocrine glands. Central nervous system (CNS) involvement is estimated to be present in 10–60% patients with pSS. The present study aimed to evaluate brainstem auditory evoked potentials (BAEP) in pSS patients without central nervous system involvement, and without otolaryngological abnormalities.MethodThirty-six pSS patients (35 women, 1 man, mean age 48 years old) and 40 healthy volunteers were investigated. BAEP, brain imaging, laboratory parameters, and clinical neurological and otolaryngological examinations were performed.ResultsAbnormal BAEP were recorded in 16.7% patients. The mean wave BAEP I and V latency and mean wave III-V and I-V interpeak latencies were significantly longer in pSS patients than the controls. There were no statistically significant correlations between BAEP parameters and laboratory tests. None of the patients was found having the abnormalities on brain imaging.ConclusionsThis study confirms that in pSS patients without clinical central nervous system impairment, auditory pathway disturbances could be found. Disorders of brain bioelectrical activity may be a consequence of ongoing autoimmune process.Key Points• BAEP abnormalities confirmed the clinically observed involvement of the central nervous system in patients with pSS.• Brain bioelectrical activity dysfunctions in pSS patients may be a consequence of ongoing inflammatory and/or immunological processes.

Central nervous system impairment detected by somatosensory evoked potentials in patients with Charcot-Marie-Tooth disease type 1A

Diseases related to peripheral myelin protein 22 (PMP22) have been implicated to involve the central nervous system (CNS). This study aimed to detect central nerve impairment using somatosensory evoked potentials (SSEPs) in patients with Charcot-Marie-Tooth disease (CMT) 1A. A total of 30 CMT1A patients and 26 healthy volunteers were included. Baseline characteristics, brain MRI and segmental SSEPs were collected from the participants. The peak latencies of N9, N13 and N20 were recorded, and central conduction velocity (CCT) was calculated and compared between groups. Significant differences were found in the peak latencies and amplitudes of N9, N13 and N20 between the two groups. CCT was significantly prolonged in the CMT group (7.05 ± 2.09 ms) compared to the control group (5.40 ± 1.79 ms) (p = 0.003). Six of 30 CMT patients had abnormal MRI signals, but no correlation with CCT was found. The central somatosensory pathway that carries SSEPs was impaired in CMT1A patients, which implies an important underlying role of PMP22 in the CNS.

CLARIFICATION OF DIAGNOSTIC CRITERIA FOR SYSTEMIC LUPUS ERYTHEMATOSUS


 The diagnostic criteria for systemic lupus erythematosus were first proposed in 1971 by the American College of Rheumatology. Though they have been revised several times (in 1982 and 1997), but, according to the information in the literary sources and our own clinical experience, the diagnosis may often be obvious, but the number of criteria is not sufficient and vice versa. This study aimed at improving diagnostic criteria for systemic lupus erythematosus (SLE). Materials and methods. 370 subjects (331 women, 89.46%, and 39 men, 10.54%, whose mean age was 41.24 ± 0.63 years) with confirmed diagnosis of systemic lupus erythematosus made up the main group. The comparison group included 234 patients (150 women, 64.10%, and 84 men, 35.90%), whose mean age was 48.82 ± 0.85 years) diagnosed to have rheumatic diseases (rheumatoid arthritis, psoriatic arthropathy). Through the period of 2010 – 2018 all the participants were subjected to comprehensive clinical laboratory and instrumental examination of all their organs and systems before starting the treatment. The obtained data were analyzed by MS Excel and SPSS by contingency tables with the calculation of diagnostic and prognostic values ​​(the relationship was considered to be significant if the absolute value of association coefficient exceeded 0.5 or the absolute value of the contingency coefficient exceeded 0.3) and Receiver Operating Characteristic-analysis. Results. The statistical analysis allowed us to identify 14 criteria comprising 18 manifestations that indicated systemic lupus erythematosus with confirmed highest sensitivity, specificity and accuracy. They include butterfly rash, photosensitivity, serous inflammation (pericarditis, pleuritis), joint pain, muscle pain, fever, alopecia, Raynaud syndrome, livedo reticularis, nervous system impairment (cramps, psychosis), thrombocytopenia, kidney damage (proteinuria, cylindruria), anti-dsDNA antibodies, antinuclear antibodies. These criteria are highly predictive; the combination of arthralgias and the presence of anti-dsDNA antibodies allows to predict the diagnosis of systemic lupus erythematosus in patients with an almost 100% certainty. To be diagnosed with systemic lupus erythematosus, patient has to meet at least three of the 14 proposed diagnostic criteria that would occur simultaneously or one after another in any period. Conclusion. We have clarified diagnostic criteria for systemic lupus erythematosus by identifying 14 criteria as follows: butterfly rash, photosensitivity, serous inflammation (pericarditis, pleuritis), joint pain, muscle pain, fever, alopecia, Raynaud syndrome, neurological disorders (cramps, psychosis), livedo reticularis, thrombocytopenia, kidney damage (proteinuria, cylindruria), anti-dsDNA antibodies, and antinuclear antibodies.

Characterisation of the cerebrospinal fluid of horses with West Nile virus neuroinvasive disease.

West Nile virus (WNV) is a zoonotic arbovirus transmitted by mosquitoes between wild birds (natural hosts) and other vertebrates. Horses and humans are incidental, dead-end hosts, but can develop severe neurological disorders. Owing to the close contact of cerebrospinal fluid (CSF) with the extracellular fluid of the brain, the analysis of CSF composition can reflect central nervous system (CNS) impairments enabling the diagnosis and understanding of various neurodegenerative CNS disorders. Our objective was to compare the findings from the CSF samples of horses with neuroinvasive WNV infection with those of healthy controls. We compared findings from fifteen CSF samples of 13 horses with acute WNV encephalomyelitis with those of 20 healthy controls. Protein, particular enzymes and ions, glucose and lactate showed abnormal levels in a significant number of WNV cases. None of the six horses with elevated glucose concentrations survived. Rather neutrophilic than mononuclear pleocytosis was identified with WNV infection. Neutrophils probably play a role in the development of inflammatory response and brain damage. Although elevated glucose levels reliably predicted the outcome, they might be the consequence of increased plasma levels and reflect general stress rather than CNS pathophysiology. The CSF findings of WNV encephalomyelitis patients are non-specific and variable but facilitate the differential diagnosis.

Cognitive assessment in patients with Hepatitis C submitted to treatment with Sofosbuvir and Simeprevir or Daclatasvir.

Hepatitis C can be defined as an infectious disease that develops an inflammatory activity, which may cause an impairment in the central nervous system, may cause cognitive impairments and symptoms of depression. The objective of this study was to verify the cognitive performance of patients with chronic hepatitis C before and after treatment with simeprevir, sofosbuvir, and daclatasvir. A prospective study was carried out in three stages: before, right after treatment, and six months after. Fifty-eight patients under clinical follow-up were evaluated at the Emílio Ribas Infectology Institute, in São Paulo, Brazil. The following instruments were used: sociodemographic questionnaire, Lawton's Scale, Beck's Depression Inventory, and a battery of neuropsychological tests that evaluated: intellectual function, memory, attention, executive function, and motor and processing speed). For statistical analysis, the analyses described (mean, frequency, and standard deviation), chi-square, and ANOVA were used. Most of the participants were male (n=30, 51.7%), with a mean of 58.23±8.79 years, mean schooling of 9.75±4.43 years. Comparing the results of neuropsychological evaluations (before, just after completion of drugs, and six months), a significant improvement was observed in relation to the acquisition of new knowledge (p=0.03), late visual memory (p=0.01), and tendency towards alternate attention (p=0.07). The treatment of the hepatitis C virus improved cognitive performance, especially in relation to memory.