Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

Abstract

Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 micromol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes.

Pronounced reversible hyperammonemic encephalopathy associated with combined valproate–topiramate therapy in a 7-year-old girl

“…Until today, the highest ammonia value of 411 mmol/l has been reported in a 47-year-old man who came up with a completely reversible valproate-induced encephalopathy. In contrast to our report, this patient’s MRI disclosed a significant brain edema followed by cerebral atrophy (Hantson et al 2005). …”

Acute Hyperammonemic Coma with Chronic Valproic Acid Therapy

“…However, in cases of profound coma and impending death, this pattern is replaced by further slowing of delta frequencies and general flattening of background activity. 8,13,14 Profound slowing and attenuation of background activity on our patient's EEG is indicative of a deep coma and correlates well with the clinical finding of decorticate posturing.…”

Valproate-Induced Hyperammonemic Encephalopathy

“…Grubben et al reported restricted diffusion on DWI in a patient with VHE discussing hyperosmolarity of the cytoplasm in astrocytes due to an excess of intracellular glutamine [3]. Hantson et al showed a case with cytotoxic edema of the cerebral cortex and vasogenic edema of the white matter and in the brain stem resembling MRI findings in patients with status epilepticus [4]. They described for the first time an involvement of the pons without decreased diffusion similar to our case.…”

“…Diffusion-weighted imaging (DWI) may show restricted diffusion [3]. Hantson et al described an involvement of the brain stem together with widespread supratentorial cortical and subcortical swelling [4]. We report a case with clinically proven VHE showing reversible hyperintense signal on MRI predominantly affecting the upper brain stem.…”