Nordstrom, Charles W.

Background: Influenza-associated encephalopathy, encephalitis, and acute necrotizing encephalopathy (ANE) are rare but potentially life-threatening neurological complications of influenza. Adult cases remain poorly characterized because the available literature is largely limited to isolated case reports and small case series. Methods: A PRISMA-guided scoping review of the MEDLINE database was conducted through 31 May 2026. Published adult cases of influenza-associated encephalopathy, encephalitis, and ANE were identified and analyzed for demographic characteristics, clinical presentation, neuroimaging findings, treatment, and outcomes. Results: Eighty-three adult cases reported between 1958 and 2026 were included. The mean age was 45.6 ± 17.8 years, and 57.8% were male. Two-thirds did not have any underlying comorbidities. Neurological symptoms developed a mean of 4.6 days after influenza onset, with influenza A accounting for 80.7% of infections. Fever (91.6%), altered mental status (86.7%), and seizures (36.1%) were the most common manifestations. Encephalitis was the predominant presentation (44.5%), followed by encephalopathy (31.3%) and ANE (24.1%). MRI most frequently demonstrated cerebral hemispheric lesions (53.0%) and bilateral thalamic involvement (36.4%), while EEG abnormalities were reported in 69.6% of patients. Overall mortality was 22.9%, highest among patients with ANE (45.0%). Among survivors, 28.9% experienced persistent neurological sequelae. Conclusions: Influenza-associated encephalopathy, encephalitis, and ANE are rare in adults but are associated with substantial morbidity and mortality. This review represents the largest adult cohort reported to date and provides important insights into the clinical spectrum, neurodiagnostic findings, and outcomes of these uncommon complications. This review highlights significant gaps in knowledge and the need for collaborative multicenter studies to improve the diagnosis, treatment, and outcome of these severe complications of influenza infection.

Background: Acute transverse myelitis (ATM) is an inflammatory disorder of the spinal cord with heterogeneous etiologies, including autoimmune, infectious, paraneoplastic, and drug-induced causes. Tumor necrosis factor-alpha (TNF-α) inhibitors have been infrequently associated with inflammatory central nervous system events, including transverse myelitis. TNF-inhibitor-associated myelitis typically presents with short-segment lesions, a normal brain MRI, and partial responsiveness to corticosteroids. Longitudinally extensive transverse myelitis (LETM) and steroid-refractory cases are uncommon. Case Presentation: A 39-year-old woman with psoriatic arthritis treated with etanercept for two years presented with subacute progressive bilateral lower-extremity sensory loss and weakness. MRI revealed a T2 hyperintense spinal cord lesion extending from T11 to L1 with gadolinium enhancement, consistent with transverse myelitis, while brain MRI was normal. Cerebrospinal fluid analysis showed lymphocytic pleocytosis, elevated protein, oligoclonal bands, and increased kappa free light chains. Extensive infectious, metabolic, paraneoplastic, and autoimmune testing, including aquaporin-4 and MOG antibodies, was negative. Despite high-dose intravenous corticosteroids and the discontinuation of etanercept, the patient experienced clinical worsening with lesion expansion, meeting criteria for LETM, and developed urinary retention. She subsequently underwent plasma exchange, resulting in radiologic improvement and moderate clinical recovery. Conclusions: This case highlights an atypical presentation of TNF-inhibitor-associated myelitis characterized by a biphasic course, longitudinally extensive spinal cord involvement, steroid refractoriness, and responsiveness to plasma exchange. These features suggest either an unusually severe TNF-inhibitor-related inflammatory phenotype or a TNF-inhibitor-triggered antibody-mediated demyelinating process. Reports of TNF-inhibitor-associated myelitis evolving into longitudinally extensive, steroid-refractory disease remain limited, and this presentation may broaden the recognized clinical spectrum of TNF-α-related CNS inflammatory events. Close neurologic follow-up and heightened awareness of severe CNS complications associated with TNF-α inhibitors are warranted.

Hepatic hydrothorax (HH) is a rare but serious complication of end-stage liver disease that is often refractory to conventional medical and procedural management. This case report describes a 75-year-old woman with HH secondary to cirrhosis from metabolic-associated steatotic liver disease. Her clinical course was marked by recurrent hospitalizations, refractory right-sided pleural effusion, and multiple unsuccessful interventions including diuretics, serial thoracenteses, an indwelling pleural catheter, and chemical pleurodesis. Notably, the persistence of pleural fluid despite resolution of ascites ultimately led to the formation of a thoracic fistula, with pleural drainage volumes exceeding 4 L/day. Further invasive procedures, such as transjugular intrahepatic portosystemic shunt or liver transplantation, were declined by the patient. She was enrolled in Mayo Clinic’s hospital-at-home (HaH) program, where continuous intravenous octreotide was initiated at a dose of 25 mcg/h. This resulted in a significant reduction in pleural output—from over 4000 mL to less than 100 mL daily. After clinical stabilization, the patient transitioned to subcutaneous octreotide and remained clinically stable for over 6 months, with improved quality of life and no significant adverse effects. To our knowledge, this is the first reported case of continuous intravenous octreotide infusion for HH administered safely in a home-based acute care setting. This case underscores the potential therapeutic role of octreotide in managing refractory HH and highlights the feasibility of delivering complex cirrhosis-related care through a HaH model with multidisciplinary collaboration. Further research is warranted to assess the long-term efficacy, safety, and cost-effectiveness of octreotide in this context and to explore broader application in home hospital environments.

Abstract Background Jamestown Canyon virus (JCV) is an emerging arboviral pathogen transmitted by mosquitoes in the United States and Canada. It is associated with neuroinvasive diseases and a wide spectrum of clinical presentations. Methods A retrospective chart review was conducted at the Mayo Clinic Health System in Northwest Wisconsin from January 2018 to December 2024, analyzing data from 12 hospitalized patients diagnosed with JCV infection. This study aimed to characterize the clinical, laboratory, imaging, and outcome profiles of the disease. The cohort included individuals aged 19 to 75 years, predominantly male (75%), with all patients reporting outdoor activity and 75% being pet owners. Results Only 27% of the patients recalled a mosquito bite. Among the cohort, 2 patients acquired an infection during the first trimester of pregnancy and subsequently delivered healthy infants. Coinfections with Borrelia burgdorferi were found in 33% of cases, while 16.7% of cases were seropositive to La Crosse virus. Magnetic resonance imaging of the brain was obtained in 5 patients and was nonspecific. Cerebrospinal fluid analysis demonstrated lymphocytic or monocytic pleocytosis in all cases where the test was performed. Conclusions All patients experienced clinical improvement, with only 1 developing lingering neurological symptoms in the form of brain fog. This study highlights the clinical heterogeneity of JCV infections and underscores the importance of including JCV in the differential diagnosis for patients residing in or traveling from endemic areas.

Background: Anaplasma phagocytophilum is an emerging tick-borne zoonotic pathogen that typically causes mild infections, which are often successfully managed in outpatient settings. Immunosuppression associated with splenectomy is a well-documented risk factor for severe infections from pathogens such as Babesia microti and encapsulated bacteria. However, splenectomy has not previously been identified as a risk factor for severe anaplasmosis. Case Presentation: This report describes a rare case of severe anaplasmosis complicated by multiorgan failure in a patient who had undergone splenectomy several decades earlier. The clinical course was notable for pneumonia, acute respiratory distress syndrome, acute kidney injury, rhabdomyolysis, atrial fibrillation, and possible myocarditis. Despite the severity of the presentation, prompt initiation of doxycycline led to recovery, albeit with a significantly prolonged hospital stay. Conclusions: Patients with splenectomy might be more likely to develop a serious form of Anaplasmosis infection such as multiorgan failure. Clinicians in tick-borne endemic areas should be aware that non-specific symptoms can indicate anaplasmosis.

Background and Objectives: Angioedema is a non-pitting edema of the submucosal layer which can be acquired or inherited and usually presents with hives. Intestinal angioedema is rare and can mimic other acute gastrointestinal disorders. It is typically associated with a lack or dysfunction of C1-inhibitor, with a small number of cases having normal C1-inhibitor function. We present a rare case of chronic recurrent intestinal angioedema in a patient with normal C1-inhibitor function who did not respond to icatibant therapy. Case presentation: A 56-year-old woman presented with 3 days of abdominal pain, nausea, vomiting, and diarrhea. She denied a history of allergies and reported a 30-year history of similar episodes requiring hospitalization. Initial evaluation demonstrated normal C4 and C1 esterase inhibitor function with negative gastrointestinal bacterial and viral panel. A CT of the abdomen and pelvis demonstrated acute diffuse bowel thickening and prominent mesenteric lymph nodes. MRI demonstrated inflammation of the small and large bowel. EGD and colonoscopy findings were normal. She was diagnosed with intestinal angioedema and started on icatibant without significant improvement. Her symptoms resolved after 3 days of supportive therapy and resolution of inflammation was noted on imaging. She was discharged home with allergy and immunology follow-up. Conclusions: Intestinal angioedema is under-recognized and presentation can overlap with other pathologies of the GI tract. Extensive work up is needed during the first episode of an attack and complement levels should be checked in all patients. Appropriate classification is important as it dictates therapy. However, ambiguous cases like ours sometimes cannot be classified into any specific category.

Hemophagocytic lymphohistiocytosis (HLH) secondary to tick-borne infections is a rare but potentially life-threatening syndrome. We performed a scoping review according to PRISMA guidelines to systematically analyze the existing literature on the topic. A total of 98 patients were included, with a mean age of 43.7 years, of which 64% were men. Most cases, 31%, were reported from the USA. Immunosuppression was present in 21.4%, with the most common cause being previous solid organ transplantation. Constitutional symptoms were the most common, observed in 83.7% of the patients, while fever was reported in 70.4% of cases. Sepsis was present in 27.6%. The most common laboratory abnormalities in this cohort were thrombocytopenia in 81.6% of patients, while anemia, leukopenia, and leukocytosis were observed in 75.5%, 55.1%, and 10.2%, respectively. Liver enzyme elevation was noted in 63.3% of cases. The H-score was analyzed in 64 patients, with the mean value being 209, and bone marrow analysis was performed in 61.2% of patients. Ehrlichia spp. was the main isolated agent associated with HLH in 45.9%, followed by Rickettsia spp. in 14.3% and Anaplasma phagocytophilum in 12.2%. Notably, no patient with Powassan virus infection or Lyme borreliosis developed HLH. The most common complications were acute kidney injury (AKI) in 35.7% of patients, shock with multiple organ dysfunction in 22.5%, encephalopathy/seizure in 20.4%, respiratory failure in 16.3%, and cardiac complications in 7.1% of patients. Treatment included antibiotic therapy alone in 43.9%, while 5.1% of patients were treated with immunosuppressants alone. Treatment with both antibiotics and immunosuppressants was used in 51% of patients. Appropriate empiric antibiotics were used in 62.2%. In 43.9% of cases of HLH due to tick-borne disease, patients received only antimicrobial therapy, and 88.4% of those recovered completely without the need for immunosuppressive therapy. The mortality rate in our review was 16.3%, and patients who received inappropriate or delayed empiric therapy had a worse outcome. Hence, we suggest empiric antibiotic treatment in patients who are suspected of having HLH due to tick-borne disease or in whom diagnostic uncertainty persists due to diagnostic delay in order to minimize mortality.

(1) Background: Cardiomyopathy in celiac disease or celiac cardiomyopathy (CCM) is a serious and potentially life-threatening disease that can occur in both adults and children. However, data supporting the causal relationship between celiac disease (CD) and cardiomyopathy (CMP) are still inconsistent. The aim of this study was to review and synthesize data from the literature on this topic and potentially reveal a more evidence-based causal relationship. (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to search Medline, Embase, and Scopus databases from database inception until September 2023. A total of 1187 original articles were identified. (3) Results: We identified 28 CCM patients (19 adult and 9 pediatric) with a mean age of 27.4 ± 18.01 years. Adult patients with CCM were predominantly male (84.2%) while pediatric patients were predominantly female (75%). The most common comorbidities associated with CCM were anemia (75%) and pulmonary hemosiderosis (20%). In 35% of patients, CCM occurred before the diagnosis of CD, while in 48% of patients, CCM and CD were diagnosed at the same time. Diagnosis of CD preceded diagnosis of CCM in only 18% of patients. Diagnosis of CCM is often delayed with an average, from the onset of symptoms to diagnosis, of 16 months. All patients were treated with a gluten-free diet in addition to guideline-directed medical therapy. At 11-month follow-up, cardiovascular improvement was seen in 60.7% of patients. Pediatric mortality was 33.3%, while adult mortality was 5.3%. (4) Conclusions: Clinicians should be aware of the possible association between CD and CMP, and we recommend CD work-up in all patients with CMP who have concomitant anemia. While we identified only 28 cases in the literature, many cases might go unreported due to a lack of awareness regarding CCM. A high degree of clinical suspicion and a prompt diagnosis of CCM are essential to minimizing the risks of morbidity and mortality, as the combination of a gluten-free diet and guideline-directed medical therapy can improve clinical outcomes.

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality worldwide, hence significant efforts have been made to establish behavior and risk factors associated with CVD. The American Heart Association proposed a 7-metric tool to promote ideal cardiovascular health (CVH). Recent data demonstrated that a higher number of ideal CVH metrics was associated with a lower risk of CVD, stroke, and mortality. Our study aimed to perform a systematic review and meta-analysis of prospective studies investigating the association of ideal CVH metrics and CVD, stroke, and cardiovascular mortality (CVM) in the general population. Medline and Scopus databases were searched from January 2010 to June 2022 for prospective studies reporting CVH metrics and outcomes on composite-CVD, coronary heart disease, myocardial infarction, stroke, and CVM. Each CVH metrics group was compared to another. Twenty-two studies totaling 3,240,660 adults (57.8% men) were analyzed. The follow-up duration was 12.0 ± 7.2 years. Our analysis confirmed that a higher number of ideal CVH metrics led to lower risk for CVD and CVM (statistically significant for composite-CVD, stroke, and CVM; p < 0.05). Conclusion: Even modest improvements in CVH are associated with CV-morbidity and mortality benefits, providing a strong public health message about the importance of a healthier lifestyle.

Anaplasma phagocytophilum is an obligate intracellular, Gram-negative pathogen, causative agent of Human Granulocytic Anaplasmosis (HGA). HGA usually manifests as a non-specific febrile illness, accompanied by evidence of leucopenia, thrombocytopenia, and an alteration in liver enzymes. Neurologic manifestations of anaplasmosis are rare and rarely reported. We describe a 62-year-old man who developed encephalitis due to an Anaplasma phagocytophilum infection. The patient favorably responded to intravenous doxycycline and recovered without neurological sequela. In the tick endemic area, clinicians should have a high index of suspicion for tick-borne diseases in patients presenting with neurological deficits. A prompt diagnosis and treatment lead to improvements in morbidity and mortality.