The diagnostic anchor in this patient was a laboratory finding rather than a physical sign: a strongly positive test for antibodies against U1 ribonucleoprotein, a component of the spliceosome, the cellular machinery that edits messenger RNA before proteins are made. High-titer anti-U1-RNP antibodies are the serological hallmark of mixed connective tissue disease, a systemic autoimmune disorder first described by Gordon Sharp and colleagues in 1972 that combines features of systemic lupus erythematosus, polymyositis, and systemic sclerosis. The condition is rare, with an estimated prevalence of roughly 3 to 37 per 100,000 people, and it disproportionately affects women. Yet the antibodies themselves can appear in patients whose disease never develops the full overlap picture, which is precisely what made this case so difficult to classify.

On admission, the clinical picture was alarming. Proximal muscle strength was graded 4 out of 5 in the deltoids and biceps but only 2 out of 5 in the hip flexors and quadriceps, meaning the patient could not raise her legs off the bed. Cranial nerves were intact, and crucially there was no rash, no Gottron’s papules, no heliotrope discoloration around the eyes, and no Raynaud phenomenon, the finger-whitening response to cold that typically signals connective tissue disease. The absence of these cutaneous and vascular stigmata is one reason the diagnosis eluded clinicians for so long. Inflammatory myopathy usually announces itself in textbooks with visible clues; here the disease confined itself almost entirely to muscle.

The laboratory numbers told a dramatic story. Serum creatine kinase, the enzyme that leaks into blood when muscle fibers rupture, measured 9,883 IU/L, roughly 68 times the upper limit of normal. Aldolase, another muscle enzyme, was similarly elevated at 75.6 U/L against a reference ceiling of 10. Inflammatory markers were high, with C-reactive protein at 116 mg/L, and the erythrocyte sedimentation rate at 67 mm/h. The extractable nuclear antigen panel revealed anti-U1-RNP antibodies at 17.67 U/mL, well above the positivity threshold of 5.0, while antibodies to Sm, Scl-70, and SS-B/La were negative and anti-dsDNA was merely equivocal, arguing against florid lupus. A positive direct Coombs test was noted but, without reticulocytosis, elevated lactate dehydrogenase, or low haptoglobin, could not be taken as proof of autoimmune hemolysis.

Electrodiagnostic testing added an important nuance. Nerve conduction studies were normal, excluding a neuropathy, but needle electromyography across ten muscles showed small, short-duration motor unit potentials with early full recruitment and, tellingly, no fibrillations or positive sharp waves. That non-irritable pattern is more characteristic of a chronic or so-called burnt-out myopathy than of florid active inflammation. The authors interpret it as the electrophysiological fingerprint of the six-year disease course, upon which the massively elevated creatine kinase indicated a fresh, biochemically active wave of muscle injury. Magnetic resonance imaging of the thighs corroborated the picture, showing diffuse T2 and STIR hyperintensity in the quadriceps consistent with muscle edema and inflammation, with no bone marrow abnormality to suggest a dystrophy or malignancy.

Treatment began within days. The patient received intravenous pulse methylprednisolone, 500 mg daily for three consecutive days, a high-dose regimen chosen because of the severity of weakness and the rapidly progressive pharyngeal dysphagia with its attendant aspiration risk. The response was rapid and unequivocal. By day four, swallowing had improved enough to restore safe oral intake, upper limb strength had returned to 5 out of 5, and lower limb strength had climbed to 4 out of 5 on the Medical Research Council scale. She was transitioned to oral prednisolone at 1 mg per kilogram per day, with methotrexate added as a steroid-sparing immunosuppressant alongside folic acid supplementation. At four-week follow-up, creatine kinase had fallen to 560 IU/L, approaching normal, and the dysphagia had not recurred.

Why did swallowing fail so suddenly? The report explains that oropharyngeal dysphagia in inflammatory myopathy arises when inflammation strikes the striated pharyngeal musculature, specifically the cricopharyngeus and the inferior pharyngeal constrictors, the muscles that coordinate the pharyngeal phase of swallowing. This feature is well recognized in polymyositis and dermatomyositis but underreported in mixed connective tissue disease, and it carries a grim prognosis when missed, being associated with aspiration, malnutrition, and death. Its abrupt emergence here, progressing from solids to liquids in roughly ten days, underscores why clinicians are urged to treat new dysphagia in any patient with myopathy as an emergency demanding immediate immunosuppression.

The classification question is where the case becomes genuinely instructive. Four sets of criteria, those of Sharp, Alarcón-Segovia and Villareal, Kasukawa and Miyawaki, and Kahn and Appeboom, are used to define mixed connective tissue disease, and all four require high-titer anti-U1-RNP antibodies. But each also demands at least one classic overlap manifestation beyond myositis: Raynaud phenomenon, swollen fingers or hands, synovitis, acrosclerosis, or sclerodactyly. This patient had none of them. Formally, therefore, she did not fulfill any of the four classification systems, and the authors designate her condition an anti-U1-RNP-positive inflammatory myopathy rather than definite mixed connective tissue disease. Such patients are increasingly viewed as occupying an early, incomplete, or myositis-dominant point on the disease spectrum, and a proportion evolve to meet full criteria over time, which is why the authors emphasize longitudinal surveillance rather than a fixed label.

The case also carries a lesson about anemia. Hematological abnormalities affect an estimated 30 to 40 percent of mixed connective tissue disease patients, and Coombs-positive hemolytic anemia has been described, yet this patient’s refractory microcytic anemia was attributed to iron deficiency for years despite supplementation failing. In retrospect, the authors write, that persistent anemia was a missed opportunity for earlier systemic evaluation. They recommend that any patient with proximal muscle weakness and unexplained, supplementation-resistant anemia undergo an autoimmune workup, including an extractable nuclear antigen panel and myositis-specific antibodies, early rather than late.

The authors acknowledge limitations: no muscle biopsy was performed to confirm the histological subtype, the burnt-out EMG pattern may simply reflect the prolonged delay, swallowing improvement was assessed clinically rather than by videofluoroscopy, and a broader myositis-specific antibody panel was not run. As a single case, the findings cannot be generalized to all populations. Still, the patient’s own account captures the stakes. She described years of declining function, sudden distress when swallowing failed, and relief at finally having a clear diagnosis after treatment restored her strength and her ability to eat normally. For clinicians, the message is blunt: autoimmune myopathy belongs on the differential for any longstanding unexplained proximal weakness, and the antibody that defines it is a simple blood test away.

Subject of Research: Anti-U1-RNP-positive inflammatory myopathy presenting with oropharyngeal dysphagia

Article Title: Anti‐U1‐RNP‐Positive Inflammatory Myopathy Presenting With Dysphagia: A Case Report

Article References: Anjlee, Rasheed, S., Ashfaq, M., Bai, S., Yaqubi, A. J., & Raza, A. A. (2026). Anti‐ U1 ‐ RNP ‐Positive Inflammatory Myopathy Presenting With Dysphagia: A Case Report. Clinical Case Reports, 14(10), Article e73676. https://doi.org/10.1002/ccr3.73676

Image Credits: AI Generated

DOI: 10.1002/ccr3.73676

Keywords: anti-U1-RNP antibodies, mixed connective tissue disease, inflammatory myopathy, dysphagia, myositis, creatine kinase, electromyography, methylprednisolone, autoimmune disease, anemia, rheumatology, case report

The parasite behind the disease has an unusual life cycle that explains why humans become accidental and unfortunate hosts. Adult worms live in the pulmonary arteries of rats, where they lay eggs that hatch into first-stage larvae. These larvae are expelled in rat faeces, then ingested by snails and slugs, which act as intermediate hosts. Within those molluscs, the larvae develop into third-stage larvae, the infectious form for humans. People typically acquire the infection by eating raw or undercooked snails, slugs, or contaminated fresh produce, or sometimes by consuming paratenic hosts such as freshwater prawns or crabs that have carried the larvae without supporting their development. Once ingested, the larvae penetrate the intestinal wall, enter the bloodstream and migrate to the central nervous system, where they die in the brain and spinal cord and trigger a fierce inflammatory response.

That inflammatory response is what defines the disease clinically. Unlike bacterial meningitis, which is dominated by neutrophils, or viral meningitis, which is dominated by lymphocytes, neuroangiostrongyliasis produces a striking influx of eosinophils, the white blood cells best known for fighting parasites and mediating allergic disease. Eosinophilic pleocytosis in the cerebrospinal fluid has long been considered the diagnostic signature of the infection, and it underpins most case definitions used in endemic regions. The headache that brings patients to hospital is typically severe and unrelenting, often accompanied by neck stiffness, and in more severe cases the migrating larvae and the inflammation they provoke can cause focal neurological deficits, paralysis, or death. There is no universally validated rapid diagnostic test in most endemic settings, and molecular confirmation by polymerase chain reaction remains unavailable in many hospitals where the disease is most common.

The Hanoi team, led by Tra Thu Doan of the Institute for Tropical Medicine at Bach Mai Hospital, assembled their series using a composite case definition. Patients had to show clinical meningitis, eosinophilia in the peripheral blood or the cerebrospinal fluid, and a reactive serum enzyme-linked immunosorbent assay for antibodies specific to A. cantonensis, with alternative diagnoses excluded. During the study period, the hospital lacked the capacity to confirm the parasite by cerebrospinal fluid polymerase chain reaction, and no patient in the series met a definite standard based on recovery of larvae or molecular detection. That limitation matters, and the authors are explicit about it: their findings describe probable cases, and the proportions they report are conditioned on the sensitivity of the case definition and of routine laboratory differentials.

The demographic and clinical profile of the 30 patients is instructive. Their mean age was 39.2 years, with a standard deviation of 17.1, and just over half, 16 of 30, were men. More than half, 17 patients, came from Nghe An or Thanh Hoa, two north-central provinces that appear to be hotspots for exposure. Headache was universal, present in all 30 patients, and neck stiffness occurred in 25, or 83.3 percent. Eleven patients, 36.7 percent, presented with focal neurological deficits, a reminder that the disease is not always a benign self-limiting headache syndrome. Exposure histories were abstracted retrospectively from routine admission notes, so the authors caution that they cannot identify a specific transmission route, though the geographic clustering points to where future surveillance should concentrate.

The laboratory findings reveal the diagnostic subtlety at the heart of the paper. Peripheral blood eosinophilia, defined as more than 8 percent eosinophils, was present in 19 of 30 patients, or 63.3 percent. But the most striking figure concerns the cerebrospinal fluid: in six patients, 20 percent of the series, no eosinophils at all were recorded on the routine differential at presentation. The authors report a 95 percent confidence interval of 9.5 to 37.3 percent for that proportion, and their conclusion is unambiguous. A normal or lymphocyte-predominant cerebrospinal fluid differential at presentation should not exclude neuroangiostrongyliasis in a patient with compatible symptoms and reactive serology. The finding echoes earlier work from northern Vietnam, including a 2020 study in PLoS Neglected Tropical Diseases that described meningitis patients with confirmed A. cantonensis infection who lacked cerebrospinal fluid eosinophilia.

Other cerebrospinal fluid parameters painted a picture of a disease that is inflammatory but rarely metabolic in the way tuberculosis meningitis can be. Hypoglycorrhachia, a low cerebrospinal fluid glucose below 2.2 millimoles per litre, was uncommon, seen in only five patients, 16.7 percent. Low cerebrospinal fluid chloride, below 120 millimoles per litre, was more frequent, present in 13 of 30 patients, or 43.3 percent, a finding that could mislead clinicians toward a diagnosis of tuberculous meningitis if interpreted in isolation. Perhaps the most encouraging laboratory trend was temporal: across serial lumbar punctures, cerebrospinal fluid cell counts, eosinophil percentages and protein levels all fell progressively, providing an objective measure of recovery that clinicians can track over the course of treatment.

Treatment in the series followed a combined approach. Every patient received albendazole, an anthelminthic drug that kills the larvae, together with methylprednisolone, a corticosteroid intended to dampen the inflammatory reaction triggered by dying parasites. This combination reflects international guidelines updated in 2021, which recommend concurrent corticosteroids with anthelminthic therapy on the theory that killing larvae without suppressing inflammation can paradoxically worsen symptoms. The outcomes were broadly favourable: 26 of 30 patients, 86.7 percent, recovered fully, three patients, 10 percent, relapsed within a six-month follow-up window, and none died. No serious adverse event was attributed to either drug. The authors are careful, however, to note that without a comparator group, no inference can be drawn about the independent contribution of either albendazole or methylprednisolone to those outcomes, a caveat that applies to virtually all published treatment data in this field.

The study’s limitations are those inherent to any retrospective case series. The case definition admits patients on peripheral eosinophilia with reactive serology alone, and the sensitivity of a routine clinical differential is imperfect, so the 20 percent figure for absent cerebrospinal fluid eosinophils is best understood as a property of this cohort and its methods rather than a universal constant. Serological tests for A. cantonensis vary in specificity, and cross-reactivity with other parasitic infections remains a concern in endemic settings. Exposure histories recorded in routine notes are a blunt instrument for epidemiology. Yet the clinical signal is consistent with a growing body of evidence from across the region, including a 2017 study in Clinical Infectious Diseases that established A. cantonensis as an important cause of eosinophilic meningitis in southern Vietnam and molecular confirmations of the parasite in cerebrospinal fluid from Laos.

For clinicians working in Vietnam and neighbouring countries, the practical messages are concrete. Neuroangiostrongyliasis should be considered in any patient with subacute severe headache and meningism, particularly when focal deficits are present, even if the cerebrospinal fluid differential shows no eosinophils on first examination. Repeat lumbar puncture may reveal the characteristic eosinophilic pleocytosis as the disease evolves, and serial measurements offer a way to monitor response. For public health authorities, the concentration of cases from Nghe An and Thanh Hoa argues for prospective surveillance and investment in molecular diagnostic capacity in the north-central provinces, where the ecological conditions that sustain the parasite, invasive Pomacea snails among them, are well documented. As the rat lungworm continues its global spread, documented as far afield as Brazil and Hawaii, the Vietnamese series adds an important data point: the disease is present, treatable, and easier to miss than its textbook description suggests.

Subject of Research: Human neuroangiostrongyliasis caused by Angiostrongylus cantonensis in northern Vietnam

Article Title: Human Neuroangiostrongyliasis Caused by Angiostrongylus cantonensis in Northern Vietnam: a Clinical–Epidemiological Case Series of Eosinophilic Response and Disease Manifestations

Article References: Thu Doan, T., Khanh Thi Nguyen, L., Minh Nong, V., Phuong Thi Ngo, N., Van Do, T., Xuan Dao, C., Xuan Do, C., & Van Vu, G. (2026). Human Neuroangiostrongyliasis Caused by Angiostrongylus cantonensis in Northern Vietnam: a Clinical–Epidemiological Case Series of Eosinophilic Response and Disease Manifestations. Acta Parasitologica, 71(5), Article 222. https://doi.org/10.1007/s11686-026-01412-z

Image Credits: AI Generated

DOI: 10.1007/s11686-026-01412-z

Keywords: Angiostrongylus cantonensis, neuroangiostrongyliasis, eosinophilic meningitis, rat lungworm, Vietnam, eosinophils, cerebrospinal fluid, albendazole, methylprednisolone, case series, parasitic disease, tropical medicine

The research, drawn from the Japan Comprehensive Process for End-of-Life Care and Organ Donation after Brain Death, or J-RESPECT, cohort, analyzed 204 brain-dead organ donors across 16 tertiary emergency and critical care centers between July 2010 and December 2023. These cases represented 21.8 percent of all brain-dead organ donations nationwide during the study period, making the dataset an unusually comprehensive window into real-world Japanese donor management. The findings were published in the journal Neurocritical Care by a team led by Tetsuya Yumoto of Okayama University, together with the J-RESPECT study group.

The physiological challenge that the study addresses is formidable. Brain death unleashes a cascade of devastating disturbances throughout the body: autonomic storm, hemodynamic collapse, hormonal deficiencies, and systemic inflammation. The loss of hypothalamic and pituitary function frequently triggers diabetes insipidus, in which the kidneys excrete enormous volumes of dilute urine, destabilizing blood pressure and fluid balance. A Korean nationwide study cited by the authors reported that cardiac arrest strikes 22.2 percent of donors during the brain death determination process itself. Every episode of cardiovascular instability threatens the viability of organs that might otherwise save lives downstream.

To combat this storm, intensivists around the world routinely deploy hormone replacement therapy, most commonly vasopressin to control diabetes insipidus and support blood pressure, and corticosteroids to stabilize hemodynamics and blunt the inflammatory response. Yet the evidence base for both practices has been surprisingly thin. A previous meta-analysis concluded that existing clinical evidence was insufficient to confirm or refute whether corticosteroids improve donor or recipient outcomes, and observational studies of vasopressin have generally evaluated the drug in isolation rather than alongside the other therapies donors typically receive.

The Japanese team set out to disentangle these overlapping treatments. Donors were classified into a high-yield group of six or more procured organs and a low-yield group of five or fewer, based on the cohort median of six organs. Lungs and kidneys were each counted as two organs when both sides were procured, while a liver counted as one even if split among multiple recipients. The researchers then applied generalized estimating equations, a statistical framework that accounts for the fact that donor management practices cluster within institutions, adjusting for age, sex, out-of-hospital cardiac arrest, admission Sequential Organ Failure Assessment score, catecholamine use, time from admission to procurement, and, critically, the number of organs the family had requested.

The results were unambiguous on one point and surprising on another. Low-dose methylprednisolone, defined as less than 15 milligrams per kilogram per day in methylprednisolone equivalents, was associated with nearly triple the odds of high-yield organ procurement compared with no corticosteroid use, with an adjusted odds ratio of 2.86 and a 95 percent confidence interval of 1.45 to 5.63. High-dose methylprednisolone at or above 15 milligrams per kilogram per day showed no such association. Vasopressin dose, categorized across four exposure levels, was not independently associated with overall organ yield after adjustment. The number of organs requested by the donor’s family was also independently linked to high-yield procurement, underscoring how consent conversations shape the eventual harvest.

In exploratory organ-specific analyses, the picture became even more nuanced. High-dose methylprednisolone was associated with dramatically higher odds of left lung donation, with an odds ratio of 8.99, while moderate-dose vasopressin was associated with lower odds of right lung donation. No consistent associations emerged for the heart, liver, or pancreas, and kidney models were not fitted because donation was nearly universal. The authors emphasize that these organ-specific findings are hypothesis-generating, particularly given the multiple comparisons performed, but they note that the lung signal is biologically plausible: corticosteroids may attenuate the inflammatory lung injury that accompanies brain death, a mechanism supported by earlier experimental and clinical work.

The study’s sensitivity analyses strengthened the central conclusion. When the yield threshold was shifted to five versus four organs, low-dose methylprednisolone remained significantly associated with the outcome, and when organ count was treated as a continuous variable, low-dose methylprednisolone was independently associated with an additional 0.46 organs procured per donor. Adjusting for the study period and replacing the admission-to-procurement interval with the brain-death-determination-to-procurement interval produced similar results. Vasopressin, by contrast, never emerged as an independent predictor of yield, suggesting that its principal benefit may lie in preserving donor physiology, controlling diabetes insipidus, and reducing catecholamine requirements rather than directly increasing the number of organs recovered.

The Japanese context adds an important dimension to the findings. The median time from hospital admission to organ procurement was 10 days, far longer than is typical in Western countries, reflecting Japan’s legally mandated process of two independent brain death determinations performed at least six hours apart, along with detailed family consent specifying which organs may be donated. During most of the study period, patients on extracorporeal membrane oxygenation could not be legally declared brain-dead under Japanese guidelines, a restriction lifted only on January 1, 2024. The scarcity of donation is itself striking: of 906 designated institutions, only 297 had ever performed a brain-dead donation procedure as of 2023, averaging roughly three cases per institution over twelve years.

The authors are careful to frame their conclusions cautiously. The study lacked recipient graft survival data, could not capture the reasons organs were not procured, and included only donors from whom at least one organ was ultimately recovered. Illness severity was adjusted only through the admission SOFA score, and variables such as target blood pressure, fluid balance, and infections were not available. Because the organ-specific analyses were exploratory and unadjusted for multiple comparisons, they require confirmation in prospective studies. Nevertheless, the message for the transplant community is clear and potentially consequential: when it comes to maximizing the gift that a brain-dead donor can give, the dose of corticosteroid may matter more than the drugs have been given credit for, and the humble low-dose regimen, rather than aggressive high-dose protocols or vasopressin titration, may be the key to unlocking more organs from every act of extraordinary generosity.

Subject of Research: Associations of vasopressin and corticosteroid therapy with organ yield in brain-dead organ donors

Article Title: Associations of Vasopressin and Corticosteroid Therapy with Organ Yield in Brain-Dead Donors: A Multicenter Cohort Study in Japan

Article References: Yumoto, T., Naito, H., Hongo, T., Obara, T., Nojima, T., Tsukahara, K., Hayakawa, M., Yokobori, S., Nishiyama, K., Atsumi, T., Tasaki, O., Yamamura, Y., Yorifuji, T., Nakao, A., and J-RESPECT study group, Tsurukiri, J., Hayamizu, M., Murahashi, S., Hayashi, M., … Hosotani, M. (2026). Associations of Vasopressin and Corticosteroid Therapy with Organ Yield in Brain-Dead Donors: A Multicenter Cohort Study in Japan. Neurocritical Care. https://doi.org/10.1007/s12028-026-02645-6

Image Credits: AI Generated

DOI: 10.1007/s12028-026-02645-6

Keywords: brain death, organ donation, organ transplantation, vasopressin, methylprednisolone, corticosteroids, hormone replacement therapy, donor management, critical care, J-RESPECT, organ yield, Japan