The blood–brain barrier becomes more permeable, leading to "vasogenic" cerebral edema (swelling of the brain due to fluid leakage from blood vessels). Large numbers of white blood cells enter the CSF, causing inflammation of the meninges and leading to "interstitial" edema (swelling due to fluid between the cells). In addition, the walls of the blood vessels themselves become inflamed (cerebral vasculitis), which leads to decreased blood flow and a third type of edema, "cytotoxic" edema. The three forms of cerebral edema all lead to increased intracranial pressure; together with the lowered blood pressure often encountered in sepsis, this means that it is harder for blood to enter the brain; consequently brain cells are deprived of oxygen and undergo apoptosis (programmed cell death).It is recognized that administration of antibiotics may initially worsen the process outlined above, by increasing the amount of bacterial cell membrane products released through the destruction of bacteria. Particular treatments, such as the use of corticosteroids, are aimed at dampening the immune systems response to this phenomenon. Diagnosis
Diagnosing meningitis as promptly as possible can improve outcomes. There is no specific sign or symptom that can diagnose meningitis and a lumbar puncture (spinal tap) to examine the cerebrospinal fluid is recommended for diagnosis. Lumbar puncture is contraindicated if there is a mass in the brain (tumor or abscess) or the intracranial pressure (ICP) is elevated, as it may lead to brain herniation.
The response was defined in the study as an increase in hemoglobin (an indirect measurement of the amount of red blood cells that are not destroyed) of 2 g/dL or greater (or to 12 g/dL or greater), and no red blood cell transfusions after the first five weeks of treatment; and no other therapies for cold agglutinin disease as defined in the study.The application for sutimlimab received orphan drug, breakthrough therapy, and priority review designations. Society and culture
Legal status
On 15 September 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Enjaymo, intended for the treatment of hemolytic anemia in adults with cold agglutinin disease (CAD). The applicant for this medicinal product is Genzyme Europe BV. Names
Sutimlimab is the International nonproprietary name (INN). References
External links
"Sutimlimab". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT03347396 for "A Study to Assess the Efficacy and Safety of BIVV009 (Sutimlimab) in Participants With Primary Cold Agglutinin Disease Who Have a Recent History of Blood Transfusion (Cardinal Study)" at ClinicalTrials.gov