When Metabolism Recovers but the Brain Does Not: A Case Report of Posterior Reversible Encephalopathy Syndrome (PRES)-Like Encephalopathy After Extreme Metformin-Associated Lactic Acidosis

Metformin-associated lactic acidosis (MALA) is a rare but life-threatening complication of metformin therapy. Neurological manifestations are usually considered reversible and are classically associated with basal ganglia involvement on magnetic resonance imaging (MRI). A 63-year-old man with previously normal renal function developed severe MALA after continuing metformin during a gastrointestinal illness. He presented with profound metabolic acidosis (pH 6.55), extreme lactate elevation to 29.9 mmol/L, acute kidney injury, and hemodynamic collapse requiring resuscitation. Toxic metformin levels confirmed the diagnosis. Despite rapid metabolic stabilization with renal replacement therapy, persistent encephalopathy remained. Serial MRI revealed bilateral cerebellar and posterior cortical vasogenic edema with contrast enhancement, without diffusion restriction, consistent with a posterior reversible encephalopathy syndrome (PRES)-like pattern. Severe cortical visual impairment persisted. This is the first detailed report describing a PRES-like radiological pattern in the setting of confirmed severe MALA without the classical lentiform fork sign. Furthermore, we report a survivor of an initial lactate level of 29.9 mmol/L - one of the highest lactate concentrations ever reported in a surviving patient. This case challenges the assumption that neurological manifestations of MALA are uniformly reversible and expands the radiological spectrum of metformin-associated brain injury. MALA may be associated with delayed and potentially irreversible toxic-metabolic brain injury despite rapid metabolic recovery. PRES-like imaging patterns can occur in metformin toxicity even in the absence of typical basal ganglia findings. This case report should raise awareness of this serious complication, encourage early neuroimaging in patients with persistent neurological symptoms, and emphasize prevention through appropriate sick-day management.

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Publication Details

Journal
Cureus
Published
2026-03-12
DOI
https://doi.org/10.7759/cureus.105129
Primary Topic
Neurological Complications and Syndromes
Type
article
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article

When Metabolism Recovers but the Brain Does Not: A Case Report of Posterior Reversible Encephalopathy Syndrome (PRES)-Like Encephalopathy After Extreme Metformin-Associated Lactic Acidosis

Joachim Schessl, M. Habs, Anna-Katharina Eser, Tobias Schmidt-Wilcke et al.
Cureus
Neurological Complications and Syndromes
article

When Metabolism Recovers but the Brain Does Not: A Case Report of Posterior Reversible Encephalopathy Syndrome (PRES)-Like Encephalopathy After Extreme Metformin-Associated Lactic Acidosis

Joachim Schessl, M. Habs, Anna-Katharina Eser, Tobias Schmidt-Wilcke, Rufat Mammadli
article en

Abstract

Metformin-associated lactic acidosis (MALA) is a rare but life-threatening complication of metformin therapy. Neurological manifestations are usually considered reversible and are classically associated with basal ganglia involvement on magnetic resonance imaging (MRI). A 63-year-old man with previously normal renal function developed severe MALA after continuing metformin during a gastrointestinal illness. He presented with profound metabolic acidosis (pH 6.55), extreme lactate elevation to 29.9 mmol/L, acute kidney injury, and hemodynamic collapse requiring resuscitation. Toxic metformin levels confirmed the diagnosis. Despite rapid metabolic stabilization with renal replacement therapy, persistent encephalopathy remained. Serial MRI revealed bilateral cerebellar and posterior cortical vasogenic edema with contrast enhancement, without diffusion restriction, consistent with a posterior reversible encephalopathy syndrome (PRES)-like pattern. Severe cortical visual impairment persisted. This is the first detailed report describing a PRES-like radiological pattern in the setting of confirmed severe MALA without the classical lentiform fork sign. Furthermore, we report a survivor of an initial lactate level of 29.9 mmol/L - one of the highest lactate concentrations ever reported in a surviving patient. This case challenges the assumption that neurological manifestations of MALA are uniformly reversible and expands the radiological spectrum of metformin-associated brain injury. MALA may be associated with delayed and potentially irreversible toxic-metabolic brain injury despite rapid metabolic recovery. PRES-like imaging patterns can occur in metformin toxicity even in the absence of typical basal ganglia findings. This case report should raise awareness of this serious complication, encourage early neuroimaging in patients with persistent neurological symptoms, and emphasize prevention through appropriate sick-day management.

Cureus
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Neurological Complications and Syndromes
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