Central and Peripheral Nervous System Manifestations Associated with Dengue Illness.

Dengue illness, caused by the dengue viruses, continues to be a major global health concern, with increasing incidence and the emergence of severe manifestations such as neurological complications. An overview of the current understanding of dengue epidemiology, clinical manifestations, and research priorities is presented here. Dengue transmission has escalated in recent years, exacerbated by factors such as vector expansion, climate change, and socioeconomic challenges. The clinical spectrum of dengue ranges from mild febrile illness to severe manifestations, including hemorrhagic fever and neurological complications. Neurological manifestations of dengue, once considered rare, are now increasingly reported, encompassing encephalitis, myelitis, and Guillain-Barré Syndrome, among others. Diagnosis primarily relies on laboratory methods such as RT/PCR, NS1 antigen detection, and serological assays. Despite advancements in understanding the dengue pathogenesis, there remains a critical need for effective vaccines, antiviral drugs, improved surveillance methods, predictive models for disease severity, and long-term studies on post-Dengue sequelae. Integrated programs and holistic approaches to dengue control are essential for mitigating its impact. Addressing these research priorities will be pivotal in combating dengue and reducing its global burden.

Primary central nervous system sarcoma with DICER1 mutation-treatment results of a novel molecular entity in pediatric Peruvian patients.

BACKGROUND: A high frequency of primary central nervous system (CNS) sarcomas was observed in Peru. This article describes the clinical characteristics, biological characteristics, and outcome of 70 pediatric patients. METHODS: Data from 70 pediatric patients with primary CNS sarcomas diagnosed between January 2005 and June 2018 were analyzed. DNA methylation profiling from 28 tumors and gene panel sequencing from 27 tumors were available. RESULTS: The median age of the patients was 6 years (range, 2-17.5 years), and 66 of 70 patients had supratentorial tumors. DNA methylation profiling classified 28 of 28 tumors as primary CNS sarcoma, DICER1 mutant. DICER1 mutations were found in 26 of 27 cases, TP53 mutations were found in 22 of 27 cases, and RAS-pathway gene mutations (NF1, KRAS, and NRAS) were found in 19 of 27 tumors, all of which were somatic (germline control available in 19 cases). The estimated incidence in Peru was 0.19 cases per 100,000 children (<18 years old) per year, which is significantly higher than the estimated incidence in Germany (0.007 cases per 100,000 children [<18 years] per year; P < .001). Patients with nonmetastatic disease (n = 46) that were treated with a combination therapy had a 2-year progression-free survival (PFS) rate of 58% (95% CI, 44%-76%) and a 2-year overall survival rate of 71% (95% CI, 57%-87%). PFS was the highest in patients treated with chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) after upfront surgery followed by radiotherapy and ICE (2-year PFS, 79% [59%-100%], n = 18). CONCLUSIONS: Primary CNS sarcoma with DICER1 mutation has an aggressive clinical course. A combination of surgery, chemotherapy, and radiotherapy seems beneficial. An underlying cancer predisposition syndrome explaining the increased incidence in Peruvian patients has not been identified so far. LAY SUMMARY: A high incidence of primary pediatric central nervous system sarcomas in the Peruvian population is described. Using sequencing technologies and DNA methylation profiling, it is confirmed that these tumors molecularly belong to the recently proposed entity "primary central nervous system sarcomas, DICER1 mutant." Unexpectedly, DICER1 mutations as well as all other defining tumor mutations (TP53 mutations and RAS-pathway mutations) were not inherited in all 19 patients where analyzation was possible. These tumors have an aggressive clinical course. Multimodal combination therapy based on surgery, ifosfamide, carboplatin, and etoposide chemotherapy, and local radiotherapy leads to superior outcomes.

BCI-Based Control for Ankle Exoskeleton T-FLEX: Comparison of Visual and Haptic Stimuli with Stroke Survivors.

Brain-computer interface (BCI) remains an emerging tool that seeks to improve the patient interaction with the therapeutic mechanisms and to generate neuroplasticity progressively through neuromotor abilities. Motor imagery (MI) analysis is the most used paradigm based on the motor cortex's electrical activity to detect movement intention. It has been shown that motor imagery mental practice with movement-associated stimuli may offer an effective strategy to facilitate motor recovery in brain injury patients. In this sense, this study aims to present the BCI associated with visual and haptic stimuli to facilitate MI generation and control the T-FLEX ankle exoskeleton. To achieve this, five post-stroke patients (55-63 years) were subjected to three different strategies using T-FLEX: stationary therapy (ST) without motor imagination, motor imagination with visual stimulation (MIV), and motor imagination with visual-haptic inducement (MIVH). The quantitative characterization of both BCI stimuli strategies was made through the motor imagery accuracy rate, the electroencephalographic (EEG) analysis during the MI active periods, the statistical analysis, and a subjective patient's perception. The preliminary results demonstrated the viability of the BCI-controlled ankle exoskeleton system with the beta rebound, in terms of patient's performance during MI active periods and satisfaction outcomes. Accuracy differences employing haptic stimulus were detected with an average of 68% compared with the 50.7% over only visual stimulus. However, the power spectral density (PSD) did not present changes in prominent activation of the MI band but presented significant variations in terms of laterality. In this way, visual and haptic stimuli improved the subject's MI accuracy but did not generate differential brain activity over the affected hemisphere. Hence, long-term sessions with a more extensive sample and a more robust algorithm should be carried out to evaluate the impact of the proposed system on neuronal and motor evolution after stroke.

Acute disseminated encephalomyelitis and COVID-19: A systematic synthesis of worldwide cases.

Acute disseminated encephalomyelitis (ADEM) has been reported after coronavirus disease 2019 (COVID-19). In this review, we systematically included worldwide reported cases on this association. We included 30 case reports (pediatric and adults) and explored epidemiological and clinical evidence. We described time to diagnosis, clinical, imaging, and laboratory features, response to treatment regimens, and differences regarding severity. Also, an original case report was presented. Neurologists must be alert to the occurrence of multifocal neurological symptoms with or without encephalopathy in patients recovered from COVID-19. Timely MRI studies should be performed to establish the diagnosis and to consider early corticosteroid-based treatment.

The moonlighting protein c-Fos activates lipid synthesis in neurons, an activity that is critical for cellular differentiation and cortical development.

Differentiation of neuronal cells is crucial for the development and function of the nervous system. This process involves high rates of membrane expansion, during which the synthesis of membrane lipids must be tightly regulated. In this work, using a variety of molecular and biochemical assays and approaches, including immunofluorescence microscopy and FRET analyses, we demonstrate that the proto-oncogene c-Fos (c-Fos) activates cytoplasmic lipid synthesis in the central nervous system and thereby supports neuronal differentiation. Specifically, in hippocampal primary cultures, blocking c-Fos expression or its activity impairs neuronal differentiation. When examining its subcellular localization, we found that c-Fos co-localizes with endoplasmic reticulum markers and strongly interacts with lipid-synthesizing enzymes, whose activities were markedly increased in vitro in the presence of recombinant c-Fos. Of note, the expression of c-Fos dominant-negative variants capable of blocking its lipid synthesis-activating activity impaired neuronal differentiation. Moreover, using an in utero electroporation model, we observed that neurons with blocked c-Fos expression or lacking its AP-1-independent activity fail to initiate cortical development. These results highlight the importance of c-Fos-mediated activation of lipid synthesis for proper nervous system development.

Cerebrospinal fluid pleocytosis as a predictive factor for CSF and plasma HIV RNA discordance and escape.

The aims of this study were to investigate the frequency of HIV-1 RNA level discordance between the cerebrospinal fluid (CSF) and plasma and of CSF viral escape (CVE) in patients with HIV-1 subtype C on antiretroviral therapy, and evaluate the CSF white blood cell (WBC) performance characteristics in predicting CSF discordance in HIV+ group and the frequency of cognitive impairment in individuals with CSF HIV discordance or escape. HIV-1 RNA levels were assessed in plasma and CSF samples from 68 HIV+ participants without opportunistic infection. CSF discordance was found in 7.4% and CVE in 10%, with comparable frequencies between HIV-1B and C. Twenty samples (29%) showed increased CSF WBC counts. This group had higher CSF and plasma HIV-1 RNA levels than the group with normal WBC counts (p < 0.0001 and 0.006, respectively). The odds of CSF discordance were 18 times higher for a person with CSF WBC count of > 5 cells/mm3 than the group with normal CSF WBC count. CSF WBC counts (cut-off of 15 cells/mm3) showed high-performance characteristics as a predictive biomarker of CSF discordance (AUC the ROC curve 0.98). The frequency of cognitive impairment for CSF escape or discordance was 83% and 80%. The odds of cognitive impairment in these groups were 19 and 15 times higher than those for an HIV(-) person. Viral discordance or escape in the CNS occurs at a comparable frequency for HIV-1C and HIV-1B. The CSF WBC count was effective as a predictive biomarker of CSF and plasma discordance.

Impact of Obesity on Lumbar Puncture Outcomes in Adults with Acute Lymphoblastic Leukemia and Lymphoma: Experience at an Academic Reference Center.

Background: Lumbar puncture (LP) is a hematology procedure that can require repeated attempts leading to traumatic LP (TLP), which has been related to the central nervous system (CNS) relapse. LP success can depend on the size and anatomy of the patient and the skill of the hematologist. The main objective was to determine the influence of body mass index (BMI) on LP outcomes. Materials and Methods: Adults with lymphoid malignancies requiring LP were included prospectively over one year; hematology residents performed most procedures. A 22-gauge Quincke needle was employed. Comparison between non-traumatic vs. traumatic LPs according to BMI, CNS relapse, and residents' year was performed. Results: Fifty-four patients with a mean age of 31.5±15.57 years were included. Diagnosis was Acute Lymphoblastic Leukemia-B (74%), Acute Lymphoblastic Leukemia-T (13%) and Non-Hodgkin Lymphoma (13%). 227 LPs were performed, 121 (53.3%) successful, 98 (43.2%) traumatic, 11 (11.2%) TLPs were macroscopically detectable and 87 (88%) microscopic; 8 (3.5%) were dry-taps. Median time between punctures was 11 days (1-202). Median BMI was 25 (22.8-39.6). Main indication for LP was prophylactic (74.5%); 39.2% were performed by first-year, 35.2% by second-year, 19.6% by third-year hematology residents. No difference (p = 0.145) for a TLP was found among residents. A BMI ≥30 (p = 0.040), non-palpable intervertebral space (p = 0.001) and more than one attempt (p = 0.001) were significant for TLP. TLP was not associated with CNS relapse (p = 0.962). Conclusion: Obesity predicted a TLP. A traumatic puncture did not increase the risk of CNS relapse at one-year follow-up.

Encefalomielitis diseminada aguda posinfecciosa en un paciente con sospecha de infección por virus dengue / Postinfectious acute disseminated encephalomyelitis in a patient with suspected dengue virus infection

Introducción: La infección por virus dengue es considerada una de las arbovirosis de mayor prevalencia en los países tropicales. La encefalomielitis diseminada aguda es un trastorno inflamatorio desmielinizante y multifocal que afecta al sistema nervioso central, de inicio agudo y curso clínico monofásico. El proceso inflamatorio se encuentra mediado por mecanismos inmunológicos y su relación con infecciones por el virus dengue aún no se establece con claridad. Objetivo: Describir un caso clínico con manifestaciones del sistema nervioso central después de una probable infección por el virus dengue. Presentación del caso: Paciente femenina de 50 años, con antecedentes de hipertensión arterial controlada. Quince días después de un cuadro de fiebre de 4 días de duración, que posiblemente fue por una infección por el virus dengue, comienza con síntomas y signos de afectación neurológica caracterizadas por ligera irritabilidad, dificultad para la concentración en una actividad específica de la vida cotidiana. Progresivamente se nota dificultad motora en el hemicuerpo izquierdo además de encontrarse agitada y distraída, motivo por el cual se decide su ingreso hospitalario. Se realiza el diagnóstico a través de los hallazgos en el examen físico, los estudios positivos de resonancia magnética nuclear y el resultado positivo de la IgM de dengue en sangre. Tanto la evolución clínica como la respuesta al tratamiento con esteroides fueron favorables. Conclusiones: El evento ocurrido en este caso sugiere que los facultativos deben tener presente el diagnóstico de encefalomielitis diseminada aguda en pacientes que han tenido infección previa o alta sospecha de esta por el virus dengue(AU)

Introduction: Dengue virus infection is one of the most prevalent arboviruses in tropical countries. Acute disseminated encephalomyelitis is an inflammatory demyelinating multifocal disorder affecting the central nervous system. Its onset is acute and its clinical course monophasic. The inflammatory process is mediated by immunological mechanisms, and its relationship to dengue virus infections is still not clear. Objective: Describe a clinical case of central nervous system manifestations after probable dengue virus infection. Case presentation: Female 50-year-old patient with a history of controlled hypertension. Fifteen days after a 4-day fever episode, possibly due to dengue virus infection, the patient starts presenting neurological signs and symptoms, such as slight irritability and difficulty to concentrate on a specific activity of daily living. The patient notices progressive motor difficulty in her left hemibody and she feels agitated and distracted. It is therefore decided for her to be hospitalized. A diagnosis is made based on physical examination findings, positive nuclear magnetic resonance studies, and the positive result of the dengue IgM blood test. Both the patient's clinical evolution and her response to treatment with steroids were favorable. Conclusions: The event herein described suggests that physicians should consider the diagnosis of acute disseminated encephalomyelitis in patients with previous infection or high suspicion of infection with dengue virus(AU)

Dispelling myths about connexins, pannexins and P2X7 in hypoxic-ischemic central nervous system.

In membrane physiology, as in other fields, myths or speculations may be repeated so often and so widely that they are perceived as facts. To some extent, this has occurred with regard to gap junctions, hemichannels, pannexin channels and P2X7 (ionotropic receptors), especially concerning the interpretation of the individual role of these channels in hypoxic-ischemic CNS since these channels may be closed by the same pharmacological blockers. Significance of existing controversial data are highlighted and contradictory views from different groups are critically discussed herein.

Patología secuelar asociada a tratamiento quirúrgico de tumores intracraneales intervenidos en el Hospital regional Teodoro Maldonado Carbo año 2014 / Sequelar pathology associated intracranial surgical treatment of tumors in the regional hospital surgery Teodoro Maldonado Carbo 2014

De la muestra de 222 pacientes operados de cirugías craneales, se identifican 49 pacientes que fueron sometidos a tratamiento quirúrgico por lesiones tumorales intracraneales cuyos resultados relevantes encontrados fueron los siguientes: los pacientes posquirúrgicos sin secuelas neurológicas representan el 47 %, el 61 % de los pacientes no necesitó tratamiento oncológico debido a presentar patología tumoral benigna, la edad promedio fue entre los 41 a 60 años; los tumores de mayor incidencia fueron los extra-axiales con un 43 %, aunque no hubo mayor diferencia predominó el sexo masculino. En cuanto a la evaluación del estado de los pacientes mediante la escala de Karnofsky entre 90 a 100, es decir pacientes que pudieron reintegrarse a su actividad laboral sin mayor inconveniente representó el 67 % de los pacientes tomados en cuenta en este estudio. De la muestra de 222 pacientes operados de cirugías craneales, se identifican 49 pacientes que fueron sometidos a tratamiento quirúrgico por lesiones tumorales intracraneales cuyos resultados relevantes encontrados fueron los siguientes: los pacientes posquirúrgicos sin secuelas neurológicas representan el 47 %, el 61 % de los pacientes no necesitó tratamiento oncológico debido a presentar patología tumoral benigna, la edad promedio fue entre los 41 a 60 años; los tumores de mayor incidencia fueron los extra-axiales con un 43 %, aunque no hubo mayor diferencia predominó el sexo masculino. En cuanto a la evaluación del estado de los pacientes mediante la escala de Karnofsky entre 90 a 100, es decir pacientes que pudieron reintegrarse a su actividad laboral sin mayor inconveniente representó el 67 % de los pacientes tomados en cuenta en este estudio. Objetivo general.- Determinar el porcentaje de pacientes con secuelas posquirúrgicas sometidos a extirpación de tumores intracraneales valorados mediante escala de Karnofsky. Objetivo específico.- Determinar porcentualmente las variables encontradas en el estudio con el fin de analizar nuestras fortalezas y amenazas ante este tipo de patologías.

Of the sample of 222 patients undergoing cranial surgery, we identified 49 patients who underwent surgical treatment for intracranial tumor lesions whose relevant results were: postoperative patients without neurological sequelae represent 47 %, 61 % of patients I did not need oncologic treatment due to enign tumor pathology, the average age was between 41 to 60 years, the tumors with the highest incidence were the extra-axial with 43 %, although there was no major difference the male gender, in terms of The evaluation of the patient's status using the Karnofsky scale between 90 and 100, that's meaning that patients who were able to return to their work without major inconvenience represented 67 % of the patients taken into account in this study. General objective.- To determine the percentage of patients with post-surgical sequelae submitted to excision of intracranial tumors evaluated by Karnofsky scale. Specific objective.- determine the variables found in the study in order to analyze our strengths and threats against this type of pathologies

Sedation and mechanical antinociception after intravenous administration of detomidine in donkeys: a dosage-effect study.

There is limited, useful, scientific information on detomidine in donkeys. This study compared the effects of intravenous saline, detomidine (10, 13.5, 17 and 20 µg/kg) and acepromazine (50 µg/kg) in donkeys by computing areas under the curve for 0-30, 30-60 and 60-120 minutes (AUC0-30, AUC30-60 and AUC60-120) for sedation scores, head heights and mechanical nociceptive thresholds (MNTs). For sedation scores, all detomidine treatments, except 10 µg/kg, increased AUC0-30 values compared with saline, and AUC0-30 values were larger for 17 µg/kg detomidine than for acepromazine. All head height AUC values were lower for detomidine than for saline (except AUC60-120 for 10 µg/kg detomidine) and acepromazine (except AUC0-30 for 10 and 20 µg/kg detomidine, and AUC60-120 for 10 µg/kg detomidine). For MNTs, all detomidine treatments increased AUC0-30 and AUC30-60 values compared with saline and acepromazine; AUC30-60 values were smaller for 10 µg/kg than for 17 and 20 µg/kg detomidine. MNT AUC60-120 values were larger for 20 µg/kg detomidine than for saline, 10 µg/kg detomidine and acepromazine. Detomidine induced sedation and antinociception, but only antinociception was dosage dependent. Selection of detomidine dosage for donkeys may depend on the required duration of sedation and/or degree of analgesia.