Gait instability and estimated core temperature predict exertional heat stroke

ObjectiveExertional heat stroke (EHS), characterised by a high core body temperature (Tcr) and central nervous system (CNS) dysfunction, is a concern for athletes, workers and military personnel who must train and perform in hot environments. The objective of this study was to determine whether algorithms that estimate Tcr from heart rate and gait instability from a trunk-worn sensor system can forward predict EHS onset.MethodsHeart rate and three-axis accelerometry data were collected from chest-worn sensors from 1806 US military personnel participating in timed 4/5-mile runs, and loaded marches of 7 and 12 miles; in total, 3422 high EHS-risk training datasets were available for analysis. Six soldiers were diagnosed with heat stroke and all had rectal temperatures of >41°C when first measured and were exhibiting CNS dysfunction. Estimated core temperature (ECTemp) was computed from sequential measures of heart rate. Gait instability was computed from three-axis accelerometry using features of pattern dispersion and autocorrelation.ResultsThe six soldiers who experienced heat stroke were among the hottest compared with the other soldiers in the respective training events with ECTemps ranging from 39.2°C to 40.8°C. Combining ECTemp and gait instability measures successfully identified all six EHS casualties at least 3.5 min in advance of collapse while falsely identifying 6.1% (209 total false positives) examples where exertional heat illness symptoms were neither observed nor reported. No false-negative cases were noted.ConclusionThe combination of two algorithms that estimate Tcr and ataxic gate appears promising for real-time alerting of impending EHS.

CNS Involvement in Hereditary Transthyretin Amyloidosis

Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is predominantly a disease of the peripheral nerves, heart, kidney, and eye. CNS involvement has been a marginal issue in research and the clinical setting until recently. Growing evidence shows that leptomeningeal amyloid accumulation is frequent and present from early stages of ATTRv amyloidosis. Several recent studies show CNS symptoms arise as a common late complication in patients with the V30M mutation after at least 14 years of symptomatic peripheral nerve disease. Conversely, in non-V30M patients, there are several descriptions, mostly case reports, of patients presenting with severe phenotypes of ocular and CNS dysfunction (oculoleptomeningeal amyloidosis), with little systemic involvement. This phenotype is found in rare families worldwide, associated with at least 14 mutations. In both patients with late and early onset CNS dysfunction, symptoms include transient focal neurologic episodes, hemorrhagic and ischemic stroke, cognitive decline, and cranial nerve dysfunction. Pathologically, there is severe amyloid deposition in the leptomeninges and cerebral amyloid angiopathy of leptomeningeal and penetrating vessels. These amyloid aggregates are formed mostly by CSF-produced transthyretin (TTR) and seem resistant to the available ATTRv therapies that increase the stability or reduce the production of plasma TTR. This indicates that CNS involvement will become a meaningful issue in patient management in upcoming years.

Neural Mechanisms of Cancer Cachexia

Nearly half of cancer patients suffer from cachexia, a metabolic syndrome characterized by progressive atrophy of fat and lean body mass. This state of excess catabolism decreases quality of life, ability to tolerate treatment and eventual survival, yet no effective therapies exist. Although the central nervous system (CNS) orchestrates several manifestations of cachexia, the precise mechanisms of neural dysfunction during cachexia are still being unveiled. Herein, we summarize the cellular and molecular mechanisms of CNS dysfunction during cancer cachexia with a focus on inflammatory, autonomic and neuroendocrine processes and end with a discussion of recently identified CNS mediators of cachexia, including GDF15, LCN2 and INSL3.

Aqueous extract of Phyllanthus niruri protects against severe malaria by blocking erythrocyte invasion and modulating the host immune response

Plasmodium falciparum parasites are the major cause of malaria across Africa. Due to the appearance of multi-drug resistant parasites, new antimalarial drugs are needed. The medicinal plant Phyllanthus niruri is being used to treat fever and other symptoms of malaria in Nigeria; however, little is known about its antimalarial mechanisms. Here, we show that aqueous extract of P. niruri (PE) has multiple antimalarial effects, including anti-parasitic and host immunomodulatory activity. We found that co-culture of P. falciparum with PE drastically reduced parasite number, but PE did not inhibit parasite development or rupture; rather, it blocked erythrocytes invasion. In addition, we identified Astragalin as one of the antimalarial compounds which are contained in PE. Moreover, we found that PE suppresses the inflammatory activity and apoptosis of immune cells (T cells) and astrocytes and neurons in the central nervous system (CNS). Furthermore, we confirmed that oral administration of PE to mice suppressed parasite growth, excessive inflammation, CNS dysfunction, and the development of experimental cerebral malaria in an in vivo murine malaria model. Our findings demonstrate that PE has multiple effects on malaria progression, targeting both parasite and host cells.

Evaluation of the Psychometric Properties of the Scale A-ONE: An Italian Cross-Sectional Study

Purpose. This study is aimed at validating the A-ONE scale in an Italian population with Central Nervous System (CNS) dysfunction. Material and Methods. Between May and November 2018, people aged between 60 and 90 with CNS dysfunction were recruited in a hospital in Rome, Italy. Patients were observed and evaluated during the activities of daily living. Internal consistency and reliability were evaluated with Cronbach’s coefficient alpha and intraclass correlation coefficient, respectively. As measured with Pearson’s correlation coefficient, the validity was examined comparing results of the A-ONE with the Barthel index. Responsiveness was evaluated 30 days after the first administration. Results. A total of 70 people having a diagnosis of neurological disorders were evaluated. The internal consistency showed Cronbach’s coefficient alpha ranging from 0.634 to 0.959. The measurement of reliability varied from 0.984 to 0.997 for intrarater and from 0.979 to 0.998 for interrater. Pearson’s correlation coefficient between the A-ONE and the Barthel index and the responsiveness showed statistically significant values ( p < 0.01 ). Conclusions. The present study provides preliminary evidence of reliability, validity, and responsiveness of the A-ONE when using elderly people with CNS dysfunction.

SARS-CoV-2 RNA in the Cerebrospinal Fluid of a Patient with Long COVID

Over 10% of COVID-19 convalescents report post-COVID-19 complications, namely, ‘long COVID’ or ‘post-COVID syndrome,’ including a number of neuro-psychiatric symptoms. The pathophysiology of COVID-19 in the central nervous system is poorly understood but may represent post-COVID injury, ongoing sterile maladaptive inflammation, or SARS-CoV-2 persistence. We describe a long COVID patient with SARS-CoV-2 RNA in the cerebrospinal fluid, which seems important, specifically due to recent reports of gray matter volume loss in COVID-19 patients. Further studies of SARS-CoV2 RNA, markers of inflammation, and neuronal damage in the CSF of patients with long COVID would be useful and should address whether the CNS can serve as a reservoir of SARS-CoV-2, clarify the pathway by which COVID-19 contributes to CNS dysfunction, and how best to therapeutically address it.

Presentations and mechanisms of CNS disorders related to COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic. In addition to severe respiratory symptoms, there are a growing number of reports showing a wide range of CNS complications in patients with COVID-19. Here, we review the literature on these complications, ranging from nonspecific symptoms to necrotizing encephalopathies, encephalitis, myelitis, encephalomyelitis, endotheliitis, and stroke. We postulate that there are several different mechanisms involved in COVID-19–associated CNS dysfunction, particularly activation of inflammatory and thrombotic pathways and, in a few patients, a direct viral effect on the endothelium and the parenchyma. Last, critically ill patients frequently present with protracted cognitive dysfunction in the setting of septic encephalopathy likely due to multifactorial mechanisms. Further studies are needed to clarify the relative contribution of each of these mechanisms, but available data suggest that CNS complications in COVID-19 are rare and probably not directly caused by the virus.

Iron Metabolism and Ferroptosis in Epilepsy

Epilepsy is a disease characterized by recurrent, episodic, and transient central nervous system (CNS) dysfunction resulting from an excessive synchronous discharge of brain neurons. It is characterized by diverse etiology, complex pathogenesis, and difficult treatment. In addition, most epileptic patients exhibit social cognitive impairment and psychological impairment. Iron is an essential trace element for human growth and development and is also involved in a variety of redox reactions in organisms. However, abnormal iron metabolism is associated with several neurological disorders, including hemorrhagic post-stroke epilepsy and post-traumatic epilepsy (PTE). Moreover, ferroptosis is also considered a new form of regulation of cell death, which is attributed to severe lipid peroxidation caused by the production of reactive oxygen species (ROS) and iron overload found in various neurological diseases, including epilepsy. Therefore, this review summarizes the study on iron metabolism and ferroptosis in epilepsy, in order to elucidate the correlation between iron and epilepsy. It also provides a novel method for the treatment, prevention, and research of epilepsy, to control epileptic seizures and reduce nerve injury after the epileptic seizure.

Scrub typhus in North India: clinical spectrum, laboratory parameters and treatment outcome in tertiary care teaching hospital

Background: Scrub typhus is an acute febrile illness causing serious complications leading to significant mortality especially if there is delay in diagnosis and treatment. It is caused by Orentia tsutsugamushi a gram negative bacterium and transmitted by the bite of the trombiculid mite (chigger). This study was undertaken to document the clinical manifestations, laboratory parameters and treatment outcomes of scrub typhus cases.Methods: This retrospective study was done in a tertiary care teaching hospital which included 40 confirmed cases of scrub typhus. The diagnosis was confirmed by positive IgM ELISA. Clinical spectrum and manifestations, laboratory parameters and course in hospital with outcomes were evaluated. Factors associated with complications and mortality were analyzed.Results: The mean age of the patients was 40 ±15 yrs with almost equal proportion of males and females (47.5 vs 52.5%). The most common presenting symptoms were Fever (100%), shortness of breath (40%), altered sensorium (22.5%), nausea/vomiting (10%), and diarrhea (7.5%). Mean duration of fever before presentation to hospital was 11.1±4.9 days. Eschar was seen in 15% of patients. Common laboratory abnormalities documented was thrombocytopenia (85%), elevated transaminases (57%) leukocytosis (45%), and leucopenia (15%). About 37.5% of patients developed multiple organ dysfunction syndrome (MODS) with case fatality rate was 10%. Acute renal failure, acute hepatitis, need of ventilator support and CNS dysfunction was higher among patient with MODS.Conclusions: Scrub typhus patients can have a wide range of manifestation ranging from mild illness to serious and life threatening complications like acute respiratory distress syndrome, acute renal failure, and acute hepatitis and CNS dysfunction. High index of suspicion with early recognition and treatment is key for good outcome. Use of empirical doxycycline may be lifesaving.

Brain injury and SARS-CoV-2 infection: Bidirectional pathways

Coronavirus infection disease (COVID-19) is a recent pandemic infectious disease caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). COVID-19 is associated with different neurological manifestations, as one-third of COVID-19 patients have some neurological disorders, including paraesthesia, headache, cold extremities and disturbances of consciousness, that are more evident in severely affected patients. The entry of SARS-CoV-2 into human host cells is mediated mainly by the cellular receptor angiotensin-converting enzyme 2 (ACE2), which is expressed at very low levels in the CNS under normal conditions. The dissemination of COVID-19 in the systemic circulation or across the cribriform plate of the ethmoid bone during an early or later phase of the infection can lead to cerebral involvement as has been reported in the past for SARS-CoV affected patients. COVID‐19‐related CNS dysfunction results from direct viral injury, indirect consequences of immune‐mediated disease, systemic effects of infection, or local effects of the virus is still a matter of debate and these hypotheses are not mutually exclusive.