Clinical, Radiologic, and Immunologic Features of Patients With CTLA4 Deficiency With Neurologic Involvement.

OBJECTIVES: CTLA4 deficiency (CTLA4d) is a disease with multisystem autoimmune features, including neurologic manifestations. We aimed to describe neurologic involvement in these patients. METHODS: We performed a cross-sectional observational study using the French Reference Centre for Primary Immunodeficiencies (CEREDIH) registry plus a surveillance in national society networks. Participants with confirmed CTLA4d and neurologic involvement were included. Clinical, laboratory, and radiologic features were collected, as well as treatments. Available MRI was double-reviewed. RESULTS: Among 70 patients with CTLA4d, 13 patients (21%) had neurologic involvement. Neurologic symptoms began at a median age of 18 [15-45] years, mostly occurring after systemic manifestations (median delay: 8.5 [4.5-10.5] years). Main symptoms included headaches, focal deficit (54% each), and seizures (38%). MRI detected at least 1 large contrast-enhancing lesion in 8 patients. Lesions reminiscent of multiple sclerosis lesions were found in 6 patients. Cerebellar (6 patients) and large spinal cord lesions (3 patients) were common. Ten patients were treated with abatacept, of whom 9 (90%) showed good clinical and radiologic response. DISCUSSION: Neurologic involvement is common among patients with CTLA4d. Despite its rarity, and considering the suspected efficacy of abatacept, neurologists should be aware of the characteristics of CTLA4d neurologic involvement.

Immunohistologic Features of Cerebral Venous Thrombosis Due to Vaccine-Induced Immune Thrombotic Thrombocytopenia.

OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia (VITT), a recently described entity characterized by thrombosis at unusual locations such as cerebral venous sinus and splanchnic vein, has been rarely described after adenoviral-encoded COVID-19 vaccines. In this study, we report the immunohistological correlates in 3 fatal cases of cerebral venous thrombosis related to VITT analyzed at an academic medical center. METHODS: Detailed neuropathologic studies were performed in 3 cases of cerebral venous thrombosis related to VITT after adenoviral COVID-19 vaccination. RESULTS: Autopsy revealed extensive cerebral vein thrombosis in all 3 cases. Polarized thrombi were observed with a high density of neutrophils in the core and a low density in the tail. Endothelial cells adjacent to the thrombus were largely destroyed. Markers of neutrophil extracellular trap and complement activation were present at the border and within the cerebral vein thrombi. SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall. DISCUSSION: Data indicate that neutrophils and complement activation associated with antispike immunity triggered by the vaccine is probably involved in the disease process.

A High Postoperative Atropinic Burden is Associated with Postoperative Delirium in Elderly Patients with Hip Fracture: Results of the Prospective, Observational, ATROPAGE Trial.

Background: Postoperative delirium frequently occurs in the elderly after hip fracture surgery and is associated with poor outcomes. Our aim was to identify a correlation between the atropinic burden (AB) due to drugs with clinical antimuscarinic effect and the occurrence of postoperative delirium. Methods: We carried out a prospective, monocentric, observational study including 67 patients over 65 years of age who underwent hip fracture surgery. The addition of the anticholinergic weight of each drug was calculated at different time points to distinguish the prehospital, intra- and postoperative part of the AB. A multivariate analysis was carried out to identify the explanatory variables associated with postoperative delirium. Results: Patients were 78 [71-86] years old. The time from admission to surgery was 12 [12-24] hours. The ADL and CIRS scores were 6 [5.5-6] and 6 [4-9], respectively. The total (prehospital plus intraoperative plus postoperative) AB was 5 [3-9]. The incidence of postoperative delirium was 54% (36/67). The demographic characteristics were comparable between delirium and no delirium groups. Univariate analysis showed statistically significant differences between no delirium and delirium groups concerning the number of prehospital atropinic drugs, prehospital AB, the number of postoperative atropinic drugs, postoperative AB, in-hospital AB and the MMSE calculated on postoperative day 5. Using multivariate analysis, postoperative AB, but not pre- and in-hospital ABs, was associated with postoperative delirium with an odds ratio of 1.84 (95% CI: 1.25-2.72; p = 0.002). A postoperative AB > 2 was associated with a postoperative delirium with an area under ROC curve of 0.73 (95% CI: 0.61-0.83; p = 0.0001). Conclusion: Contrary to a prior exposure to atropinic drugs, a postoperative atropinic burden >2 was associated with postoperative delirium in elderly patients with hip fracture. Postoperative administration of (new) antimuscarinic drugs is a precipitating factor of delirium that could be avoided.

Pulmonary mucormycosis following autologous hematopoietic stem cell transplantation for rapidly progressive diffuse cutaneous systemic sclerosis: A case report.

RATIONALE: The use of autologous hematopoietic stem cell transplantation (AHSCT) for autoimmune diseases has become the first indication for transplant in nonmalignant disease. Mucormycosis is a rare invasive infection with increasing incidence in patients treated with AHSCT. We report the first case of pulmonary mucormycosis following AHSCT for systemic sclerosis (SSc). PATIENT CONCERNS: A 24-year-old woman with rapidly progressive diffuse cutaneous SSc presented with an acute respiratory distress syndrome 6 days after AHSCT. DIAGNOSES: The results of clinical and computed tomography scan were consistent with pulmonary mucormycosis and the diagnosis was confirmed by a positive Mucorales Polymerase Chain Reaction on a peripheral blood sample. INTERVENTIONS AND OUTCOMES: Early antifungal therapy by intravenous amphotericin B provided rapid improvement within 4 days and sustained recovery after 2 years of follow-up. LESSONS: With the progressively increasing use of AHSCT and other stem cell therapy for treatment of severe SSc and other autoimmune diseases, the potential onset of rare post-transplant fungal infections, such as mucormycosis, requires careful patient monitoring and better awareness of early initiation of adequate therapy.