Report of severe accidental baclofen intoxication in a healthy 4-year-old boy and review of the literature.

The number of reports on baclofen intoxication has increased in recent years. Here we report the case of a 4-year-old boy in deep coma who was referred to the pediatric intensive care unit. The patient was intubated and mechanically ventilated. A computerized tomography scan without contrast showed a collapsed appearance of the ventricular system suggesting diffuse cerebral edema. A multichannel electroencephalogram registered 6 h after admission showed a very slow and ample continuous pattern, without structure, nonreactive to stimulations, expressing diffuse and severe nonspecific cerebral pain. A targeted analysis to determine the baclofen plasma levels was performed. Test results of plasma samples were highly positive for baclofen (2009 ng/mL). Following 36 h of mechanical ventilation, the patient rapidly regained consciousness and recovered normal neurological behavior. The present case demonstrates the importance of considering baclofen overdosage in cases of deep coma with areflexia, and emphasizes the importance of warning parents about the potential toxicity of baclofen when prescribing the drug to a family member. A review of the literature on pediatric baclofen overdose is included.

Renal Operational Tolerance Is Associated With a Defect of Blood Tfh Cells That Exhibit Impaired B Cell Help.

Renal operationally tolerant patients (TOL) display a defect in B cell differentiation, with a deficiency in plasma cells. Recently described, T follicular helper (Tfh) cells play a critical role in B cell differentiation. We analyzed blood Tfh subsets in TOL and transplanted patients with stable graft function under immunosuppression (STA). We observed a reduced proportion of blood activated and highly functional Tfh subsets in TOL, without affecting Tfh absolute numbers. Functionally, Tfh cells from TOL displayed a modified gene expression profile, failed to produce interleukin-21, and were unable to induce IgG production by naive B cells. This Tfh defect is linked to a low incidence of postgraft de novo donor-specific antibody (dnDSA) immunization, suggesting that the lack of Tfh cells in TOL may induce a protolerogenic environment with reduced risk of developing dnDSA. Finally, we showed that elevated Tfh in STA precedes the occurrence of dnDSA during an alloresponse. These data provide new insights into the mechanisms of antibody response in operational tolerance. Disrupted homeostasis and impaired Tfh function in TOL could lead to a reduced risk of developing dnDSA and suggest a predictive role of blood Tfh cells on the occurrence of dnDSA in transplant recipients.