Predicting SILENT after lithium poisoning: a multicenter cohort study and pragmatic risk stratification model

INTRODUCTION: The Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) is a rare but potentially devastating complication of lithium poisoning. Current evidence rests on case reports and small series, leaving its true incidence, risk factors, and follow-up tools poorly defined. METHODS: Retrospective, international, multicenter cohort of adults evaluated for lithium poisoning (2015-2022) across 23 tertiary hospitals in Spain, Ireland, and Switzerland. SILENT was defined as persistent neurological sequelae attributed to lithium toxicity documented at 60 days. A parsimonious multivariable logistic regression model was built from routinely available clinical variables and assessed by ROC analysis and internal split-sample validation. RESULTS: Among 644 episodes, SILENT was identified in 49 (7.6%); predicted probabilities were available for 456 episodes (39 SILENT cases). Affected patients were older and more often had acute-on-chronic poisoning, early neurological manifestations, and greater clinical severity. Serum lithium concentrations were not associated with SILENT. The model-age, poisoning type, neurological findings (ataxia/myoclonus), Poisoning Severity Score, and peak urea-showed good discrimination (AUC 0.813; 95% CI 0.743-0.882) and acceptable internal validation (AUC 0.730; 95% CI 0.572-0.888). A sensitivity-oriented threshold (P≥0.0475) yielded a high negative predictive value (98.2%), supporting its use to prioritize post-discharge neurological follow-up. DISCUSSION: SILENT occurred more frequently than case-based literature suggests and followed a recognizable presentation pattern. Serum lithium alone did not predict long-term sequelae. The model, based on routine variables, may offer a pragmatic tool for early risk stratification. CONCLUSION: SILENT is not an exceptional outcome after lithium poisoning and cannot be predicted by serum lithium alone. A simple clinical prediction model may identify patients warranting structured neurological follow-up. External validation is required before implementation.

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Journal
Clinical Toxicology
Published
2026-09-07
DOI
https://doi.org/10.1080/15563650.2026.2693677
Primary Topic
Bipolar Disorder and Treatment
Type
article
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article

Predicting SILENT after lithium poisoning: a multicenter cohort study and pragmatic risk stratification model

Neus Rodríguez Farré, Beatriz Martín-Pérez, Belén Ruíz‐Antorán, Santiago Nogué et al.
Clinical Toxicology
Bipolar Disorder and Treatment
article

Predicting SILENT after lithium poisoning: a multicenter cohort study and pragmatic risk stratification model

Neus Rodríguez Farré, Beatriz Martín-Pérez, Belén Ruíz‐Antorán, Santiago Nogué, August Supervía, Luca Cioccari, Antonio F Caballero-Bermejo, Jordi Puiguriguer-Ferrando, Héctor Hernández Ontiveros, Xavier Canseco Suárez, Ruadhan O’Laoi, Alberto Cózar-Llistó, Emilio Salgado, Mikel Urroz, Isabel Llopis Sanmillan, Valle Molina Samper, Francisca Córdoba, Blanca Andrea Gallardo Sánchez, Natalia Sanz-López, M. Àngels Gispert-Ametller, Edith Gutierrez, Marina Vergara Ortiz, Pablo Navarro Román, Álvaro Pineda-Torcuato, Carolina Sánchez, Susanna Vert García, María del Pilar Gómez Jiménez, Victoria Lobo-Antuña, Paula Romero Gallardo, Cormack Kennedy, Sandra Mora Azabal, Guillermo Burillo-Putze, Macarena Lucila Míguez del Águila, Benjamín Climent, Andrea Terron Sánchez, Francisco J. Callado Moro
article en

Abstract

INTRODUCTION: The Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) is a rare but potentially devastating complication of lithium poisoning. Current evidence rests on case reports and small series, leaving its true incidence, risk factors, and follow-up tools poorly defined. METHODS: Retrospective, international, multicenter cohort of adults evaluated for lithium poisoning (2015-2022) across 23 tertiary hospitals in Spain, Ireland, and Switzerland. SILENT was defined as persistent neurological sequelae attributed to lithium toxicity documented at 60 days. A parsimonious multivariable logistic regression model was built from routinely available clinical variables and assessed by ROC analysis and internal split-sample validation. RESULTS: Among 644 episodes, SILENT was identified in 49 (7.6%); predicted probabilities were available for 456 episodes (39 SILENT cases). Affected patients were older and more often had acute-on-chronic poisoning, early neurological manifestations, and greater clinical severity. Serum lithium concentrations were not associated with SILENT. The model-age, poisoning type, neurological findings (ataxia/myoclonus), Poisoning Severity Score, and peak urea-showed good discrimination (AUC 0.813; 95% CI 0.743-0.882) and acceptable internal validation (AUC 0.730; 95% CI 0.572-0.888). A sensitivity-oriented threshold (P≥0.0475) yielded a high negative predictive value (98.2%), supporting its use to prioritize post-discharge neurological follow-up. DISCUSSION: SILENT occurred more frequently than case-based literature suggests and followed a recognizable presentation pattern. Serum lithium alone did not predict long-term sequelae. The model, based on routine variables, may offer a pragmatic tool for early risk stratification. CONCLUSION: SILENT is not an exceptional outcome after lithium poisoning and cannot be predicted by serum lithium alone. A simple clinical prediction model may identify patients warranting structured neurological follow-up. External validation is required before implementation.

Clinical Toxicology
Universidad de La Laguna (ES), Universitat Pompeu Fabra (ES), Trinity College (CA), Trinity College Dublin (IE), Hospital Universitario de Canarias (ES), Hospital Universitario La Paz (ES), University Hospital of Bern (CH), Hospital de Sant Pau (ES), University Hospital Complex Of Vigo (ES), Universidad Nebrija (ES), Hospital Universitario de Torrejón (ES), Hospital de Viladecans (ES), Hospital Universitario 12 De Octubre (ES), Fundación Española de la Nutrición (ES), Hospital Universitario de Getafe (ES), Hospital Universitario Puerta de Hierro Majadahonda (ES), Hospital Clínic de Barcelona (ES), Hospital Universitario de Burgos (ES), Navarrabiomed (ES), Hospital General Universitario De Valencia (ES), Hospital Juan Ramón Jiménez (ES), Hospital Del Mar (ES), Hospital de Sant Joan Despí Moisès Broggi (ES), Parc de Salut (ES), Hospital Universitario Son Espases (ES), St. James's Hospital (IE), Hospital Universitari de Girona Doctor Josep Trueta (ES), Hospital Universitario Río Hortega (ES), Hospital Universitario Severo Ochoa (ES), Kantonsspital Aarau (CH), Hospital Universitario Ramón y Cajal (ES), Universidad Autónoma de Madrid (ES), Universitat de Barcelona (ES)
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Bipolar Disorder and Treatment
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