Case Report: Disseminated Strongyloidiasis in a Patient with COVID-19.

The SARS-CoV-2 virus has emerged and rapidly evolved into a current global pandemic. Although bacterial and fungal coinfections have been associated with COVID-19, little is known about parasitic infection. We report a case of a COVID-19 patient who developed disseminated strongyloidiasis following treatment with high-dose corticosteroids and tocilizumab. Screening for Strongyloides infection should be pursued in individuals with COVID-19 who originate from endemic regions before initiating immunosuppressive therapy.

Molecular, immunological and neurophysiological evaluations for early diagnosis of neural impairment in seropositive leprosy household contacts.

BACKGROUND: Household contacts constitute the highest risk group for leprosy development, and despite significant progress in the disease control, early diagnosis remains the primary goals for leprosy management programs. METHODS: We have recruited 175 seropositive and 35 seronegative household contacts from 2014 to 2016, who were subjected to an extensive protocol that included clinical, molecular (peripheral blood qPCR, slit-skin smear qPCR, skin biopsy qPCR) and electroneuromyographic evaluations. RESULTS/PRINCIPAL FINDINGS: The positivity of peripheral blood qPCR of seropositive contacts was 40.6% (71/175) whereas only 8.6% (3/35) were qPCR positive in seronegative contacts (p = 0.0003). For the slit-skin smear, only 4% (7/175) of seropositive contacts presented positive bacilloscopy, whereas the qPCR detected 47.4% (83/175) positivity in this group compared with only 17.1% (6/35) in seronegative contacts (p = 0.0009). In the ENMG evaluation of contacts, 31.4% (55/175) of seropositives presented some neural impairment, and 13.3% (4/35) in seronegatives (p = 0.0163). The presence of neural thickening conferred a 2.94-fold higher chance of ENMG abnormality (p = 0.0031). Seropositive contacts presented a 4.04-fold higher chance of neural impairment (p = 0.0206). The peripheral blood qPCR positivity presented odds 2.08-fold higher towards neural impairment (OR, 2.08; p = 0.028). Contrarily, the presence of at least one BCG vaccine scar demonstrated 2.44-fold greater protection against neural impairment (OR = 0.41; p = 0.044). CONCLUSIONS/SIGNIFICANCE: ELISA anti-PGL-I is the most important test in determining the increased chance of neural impairment in asymptomatic leprosy household contacts. The combination of the two assays (ELISA anti-PGL-I and peripheral blood qPCR) and the presence of BCG scar may identify individuals with higher chances of developing leprosy neuropathy, corroborating with the early diagnosis and treatment.

Sensory neuronopathy heralding human T cell lymphotropic virus type I myelopathy.

Neurological phenotypes of human T cell lymphotropic virus type I (HTLV-1) are numerous and rarely may not manifest the classic HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We report a case of HTLV-1-related sensory neuronopathy heralding the classic HAM/TSP.

Aluminum exposure for 60days at an equivalent human dietary level promotes peripheral dysfunction in rats.

Aluminum (Al) is a neurotoxic associated with a number of chronic human diseases. We investigated the effects of Al exposure at doses similar to human dietary levels and at a high level exposure to Al on the peripheral nervous system. Wistar male rats were divided into two major groups and received orally: 1) First group - Low level - rats were subdivided and treated for 60days: a) Control - received ultrapure water; b) AlCl3 - received Al at 8.3mg/kg body weight (bw) for 60days; and 2) Second group - High level - rats were subdivided and treated for 42days: C) Control - received ultrapure water through oral gavage; d) AlCl3 - received Al at 100mg/kg bw for 42days. Von Frey hair test, plantar test, the presence of catalepsy and the spontaneous motor activity were investigated. Reactive oxygen species, lipid peroxidation and total antioxidant capacity, immunohistochemistry to investigate the nerve inflammation and, the specific presence of Al in the sciatic nerve fibers were investigated. Al exposure at a representative human dietary level promotes the development of mechanical allodynia, catalepsy, increased inflammation in the sciatic nerve, systemic oxidative stress and, is able to be retained in the sciatic nerve. The effects of low-dose Al were similar to those found in rats exposed to Al at a dose much higher (100mg/kg). Our findings suggest that Al may be considered toxic for the peripheral nervous system, thus inducing peripheral dysfunction.

Antiallodynic effect of ß-caryophyllene on paclitaxel-induced peripheral neuropathy in mice.

Painful peripheral neuropathy is a common side effect of paclitaxel (PTX). The use of analgesics is an important component for management of PTX-induced peripheral neuropathy (PINP). However, currently employed analgesics have several side effects and are poorly effective. ß-caryophyllene (BCP), a dietary selective CB2 agonist, has shown analgesic effect in neuropathic pain models, but its role in chemotherapy-induced neuropathic pain has not yet been investigated. Herein, we used the mouse model of PINP to show the therapeutic effects of BCP in this neuropathy. Male Swiss mice receiving PTX (2 mg kg-1, ip, four alternate days) were treated with BCP (25 mg kg-1, po, twice a day) either during or after PTX administration. Some groups were also pretreated with AM630 (CB2 antagonist, 3 mg kg-1, ip) or AM251 (CB1 antagonist, 1 mg kg-1, ip). Spinal cord samples were collected in different time points to perform immunohistochemical analysis. BCP attenuated the established mechanical allodynia induced by PTX (p < 0.0001) in a CB2-dependent manner. Of note, when given concomitantly with PTX, BCP was able to attenuate the development of PINP (p < 0.0001). Spinal cord immunohistochemistry revealed that preventive treatment with BCP reduced p38 MAPK and NF-κB activation, as well as the increased Iba-1 and IL-1ß immunoreactivity promoted by PTX. Our findings show that BCP effectively attenuated PINP, possibly through CB2-activation in the CNS and posterior inhibition of p38 MAPK/NF-κB activation and cytokine release. Taken together, our results suggest that BCP could be used to attenuate the establishment and/or treat PINP.

Autoimmune neuropathies associated to rheumatic diseases.

Systemic manifestations are frequent in autoimmune rheumatic diseases and include peripheral nervous system damage. Neuron cell body, axons and myelin sheath may all be affected in this context. This involvement results in severe and sometimes disabling symptoms. Sensory, motor and autonomic features may be present in different patterns that emerge as peculiar clinical pictures. Prompt recognition of these neuropathies is pivotal to guide treatment and reduce the risks of long term disability. In this review, we aim to describe the main immune-mediated neuropathies associated to rheumatic diseases: sensory neuronopathies, multiple mononeuropathies and chronic inflammatory demyelinating polyradiculoneuropathy, with an emphasis on clinical features and therapeutic options.

Charcot's arthropathy secondary to herpetic encephalitis sequelae: an unusual presentation.

Neuropathic arthropathy (Charcot's arthropathy) is a progressive articular disease associated with a reduced sensorial and protector proprioceptive reflex. Its etiology includes many different conditions such as syringomyelia, traumatic lesion causing medullary deformity, spina bifida, diabetic neuropathy, leprosy neuropathy, neurofibromatosis, amyloid neuropathy, alcohol, and repetitive injection of hydrocortisone into joints, among others. However, the relationship between Charcot's arthropathy and herpetic encephalitis has not yet been described. Herpes encephalitis causes acute and chronic diseases of the peripheral or central nervous system. It can manifest as subacute encephalitis, recurrent meningitis, or myelitis. It can also resemble psychiatric syndromes, diplopia, sensory changes in the face and limbs, personality changes, frontal dysexecutive syndrome, stiff neck, subclinical alterations of the vestibular function, intracranial hypertension, convulsion, hemiparesis, and generally includes motor components, among others. On the other hand, pure peripheral sensory disturbance has not been described. In this article, we report the clinical case of a patient with Charcot's arthropathy secondary to pure peripheral sensory polyneuropathy as a consequence of progressive herpetic encephalitis sequelae. In this article, the authors report the first case of Charcot's arthropathy secondary to herpetic encephalitis.

Prevalence and characteristics of immunomediated neuropathies in a group of patients with autoimmune diseases.

OBJECTIVE: To determine the prevalence and the clinical-neurophysiological characteristics of immunomediated peripheral neuropathies (PN) in a group of patients with systemic autoimmune diseases. METHOD: Fifty-nine patients with proved systemic autoimmune diseases were included. Patients underwent clinical examination and nerve conduction studies to diagnose the PN. RESULTS: Immune PNs were detected in 18 patients (30.5%). Out of the total number of PNs (18), 39% were sensory-motor polyneuropathies, 33% mononeuritis multiplex, 11% pure sensory polyneuropathies, 11% cranial neuropathies, and 6% proximal motor neuropathies, such as the Guillain-Barré syndrome. Nine PNs (50%) appeared at the onset of the connective tissue disorders, and the rest of the cases appeared during the course of the disease. Of the total of PNs detected in this study, only 45% had a previous diagnosis. Vasculitis was the disease that presented more associated PNs. Systemic lupus erythematosus showed the widest range of PN clinical varieties. CONCLUSIONS: The first national prevalence rate of PNs in patients with systemic autoimmune diseases was provided: 30.5%. No comparative data were found in the international bibliography. Sensory-motor polyneuropathy was the most frequently observed form of PN, followed by mononeuritis multiplex. The NPs appeared with the same frequency both at the onset and during the course of the diseases under study; these predominated at the onset of vasculitis and primary Sjögren syndrome. The compromise of the peripheral nervous system is underdiagnosed.

Peripheral neuropathy in HTLV-I infected individuals without tropical spastic paraparesis/HTLV-I-associated myelopathy.

Tropical spastic paraparesis/ HTLV-I-associated myelopathy (TSP/HAM) is the classical neurological manifestation of HTLV-I. Only a few studies have described isolated peripheral neuropathy (PN) among HTLV-I infected individuals. 335 infected individuals without TSP/HAM were evaluated for the presence of PN and 45 of them showed evidences of peripheral nervous system involvement. Of these 21 patients had isolated PN, defined by clinical and/or electrophysiological criteria. Sural nerve biopsies revealed inflammatory infiltrates in 2, axonal degeneration in 2 and segmental demyelination in 1. Therefore, peripheral neuropathy can be found as an isolated manifestation of HTLV-I infection. We conclude that HTLV-I infection should be investigated in patients with PN of unknown origin.

Increase in asialoganglioside- and monosialoganglioside-reactive antibodies in chronic Chagas' disease patients.

Antibodies reactive with the core glycan of asialoganglioside (GA1), monosialoganglioside (GM1), and disialoganglioside (GD1a) were studied in human sera. In healthy individuals, GA1-, GM1-, and GD1a-reactive antibodies were mainly of the IgM class, but also of the IgA and IgG classes, and were present at low titers in the serum of 68%, 79%, and 91% of the individuals studied, respectively. Levels of anti-GA1 and anti-GM1 antibodies, mainly of the IgA and IgG classes, were significantly elevated (P < 0.001) in 62% and 72% of subjects, respectively, chronically infected with Trypanosoma cruzi, with no association found with the degree of myocardial damage. No significant increase in anti-GA1 and anti-GM1 antibodies was found in dilated cardiomyopathy patients. The level of anti-GD1a antibody was not significantly different between healthy controls and chronic chagasic or dilatatory cardiomyopathy patients. Since the peripheral nervous system is very rich in gangliosides, it is possible that the increases in GA1- and GM1-specific antibodies that develop during chronic T. cruzi infection are involved in the pathology of peripheral neuropathy in Chagas' disease.

Anti-GM1 ganglioside IgM-antibodies present in human plasma: affinity and biological activity changes in a patient with neuropathy.

Low affinity anti-GM1 IgM-antibodies are part of the normal repertoire of human plasma antibodies (Mizutamari et al.: J Neuroimmunol 50:215-220, 1994), a fact that is against the pathological role proposed for them in autoimmune diseases. Here we present evidence that these low affinity IgM-antibodies are devoid of complement-mediated lytic activity to GM1-liposomes, suggesting that they should not be considered harmful. In contrast to the absence in normal individuals, in the plasma of a patient with sensory polyneuropathy we detected high affinity anti-GM1 IgM-antibodies. Concomitant with the presence of these high affinity anti-GM1 IgM-antibodies, the patient plasma is capable of producing complement-mediated lysis of GM1-liposomes. These results suggest that an increase in the affinity of the naturally existing anti-GM1 antibodies could be the trigger that switches them from non-harmful to pathological.

[New evidence of the antigenic relation between the viruses of epidemic neuropathy and the human nervous system. A study of the immune cellular response in patients with epidemic neuropathy and controls. A review of the topic]. / Nuevas evidencias de la relación antigénica entre los virus de la neuropatía epidémica y el sistema nervioso humano. Estudio de la respuesta inmune celular en pacientes con neuropatía epidémica y controles. Revisión del tema.

A series of experiments was made at the Virology Department of the "Pedro Kourí" Institute of Tropical Medicine aimed at obtaining new evidences on the possible antigenic relations existing between the viruses isolated from patients with epidemic neuropathy and the structures of the human nervous system. According to the results it may be finally inferred that the persistence and/or autoimmunity may be considered as mechanisms through which the studied viruses participate in the etiopathogenesis of the epidemic neuropathy in Cuba. For future experiments it is very important to identify the possible viral epitopes involved in the molecular mimicry that are responsible for the probable autoimmune mechanisms or for the viral persistence.

[Epidemic neuropathy. An etiopathogenetic hypothesis]. / Neuropatía epidémica. Hipótesis etiopatogénica.

An etiopathogenic hypothesis is explained taking into consideration the most significant results of the research performed on neuropathy as well as the latest knowledge about the infections produced by Enterovirus. The hypothesis allows to make a logical interpretation of these results; however, the new aspects included make it controversial in the light of the present knowledge to pathogeny by Enterovirus. Further research is needed to confirm this hypothesis.

[Possible role of the immune system in lead peripheral polyneuropathy. Case report]. / Possível intermediação do sistema imune na polineuropatia periférica plúmbica. Relato de caso.

This is a case report of a twenty-five years old man who developed, due to lead intoxication, a severe axonal peripheral predominantly motor neuropathy, after a shotgun injury. The projectile was retained in the right hip. Before this diagnosis had been done he was treated with corticosteroids in immunosuppressive doses and showed an improvement, but he had worsened at each attempt to interrupt the drug. Because he had also other signs of lead intoxication, such as abdominal cramps, severe anemia and seizures it was search for the blood levels of lead that was 101.2 micrograms/dl. The patient was treated with calcium disodium edetate and surgical removal of lead fragments. After that he had a good outcome with no need of corticosteroids. It is emphasized the possible relevance of the immune system on the mechanism of plumbic intoxication and the importance of the withdrawal of the lead material retained in joints.

Possível intermediaçäo do sistema imune na polineuropatia periférica plúmbica: relato de caso / Possible role of the immune system in lead neuropathy: case report

Relata-se o caso de paciente de 25 anos com ferimento porarma de fogo na articulacao coxofemural esquerda que desenvolveu, entre outros sinais de intoxicacao plumbica, polineuropatia periferica axonal predominantemente motora. Tratado inicialmente com corticosteroides em doses imunossupressoras obteve melhora, mas apresentava recidiva a cada tentativa de retirada da medicacao. Demonstrados laboratorialmente niveis sericos toxicos de chumbo, foi submetido a quelacao com EDTA e a retirada cirurgica do projetil, com boa recuperacao dapolineuropatia, sem necessidade ulterior de corticosteroides. Enfatiza-se: 1) o possivel papel do sistema imune na fisiopatogenia da intoxicacao por chumbo, podendo ser um dos motivos das diferentes apresentacoes clinicas das neuropatias plumbicas na infancia e no adulto; 2) a importancia da retirada do material plumbeo quando alojado em articulacoes.

[Western blot study of sera from patients with epidemic neuropathy]. / Estudio por western blot de sueros de pacientes con neuropatía epidémica.

The immune response of a group of patients with epidemical neuropathy and of controls was studied by the immunoblotting technique against proteins of the Coxsackie virus and the proteins of slow effect isolated in our laboratory. 13 sera of patients with epidemical neuropathy and 9 sera of controls were studied. Of the 13 sera studied, 8 (61.5%) recognized protein VPI and 2 sera (15.3%) protein VP0 of the strain 47.93. Of the 9 controls studied, 4 (44.4%) recognized protein VPI and 3 (33.3%) protein VP0 only. With the antigen prepared from the slow effect strain it was obtained a specific signal in 5 (38.5%) sera of patients and in 2 sera (22.5%) of controls. It should be stressed that in this last case the protein observed had a molecular weight of 41,300 D, and that its size was smaller than that of the preceding protein detected against the strain 47.93 was of 45,000 D.

[Mechanism of Enterovirus participation in epidemic neuropathy. Physiopathological hypothesis]. / Mecanismo de participación de los Enterovirus en la neuropatía epidémica. Hipótesis fisiopatológicas.

During the epidemic neuropathy occurred in Cuba from 1992 to 1993, viral isolations antigenically connected with Coxsackie viruses were obtained from the cerebrospinal fluid of patients. Virological, epidemiological, toxicologic, nutritional, immunological and histopathological investigations were made. Though the disease was related to toxic and nutritional factors, it has been impossible to identify the cause of the epidemic. Taking into consideration the results of the different investigations, we have formulated a comprehensive and multifactorial hypothesis to explain the physiopathological mechanism of the participation of the isolated viruses as mediators in a process of autoimmunity of the pathogeny of the disease.

[Cuban epidemic neuropathy. III. Neutralizing antibodies to the strains isolated and to other enteroviruses in patients and healthy subjects]. / Neuropatía epidémica cubana. Parte III. Anticuerpos neutralizantes a cepas aisladas y otros Enterovirus en pacientes y personas sanas.

Determinations of neutralizing antibodies to the strain 47/93 IPK (CA9) and to the strain 590 were performed in serum samples from patients presenting with epidemic neuropathy and from a group of seemingly healthy subjects. Determinations were also done in the reference strains CA9 and CB1-6 by the microneutralization technique. Patients and their contacts showed significantly higher percentages of neutralizing antibodies to the strain 47/93 than the control group and residents of municipalities with a low rate of the disease. This difference was also confirmed regarding the geometric mean titres with the use of the reference strains CA9 and CB2-4. An increased circulation of the strain 47/93 within the infantile population from 1981 to 1993 was evidenced. Patients exhibited significantly lower percentages and geometric mean titres of neutralizing antibodies to the strain 590 than the control group, despite the fact that in 25/28 certain agents having a mild cytopathogenic effect had been isolated. The possibility of two mechanism of neutralization is stated and an hypothesis on the mechanism by which these viruses may be involved in the pathophysiology of the disease is formulated.