Memory impairment with symmetrical hippocampal lesions following acute glufosinate-ammonium intoxication

Description

A male patient in his 60s, with a previous diagnosis of depression, was admitted to the emergency department after an intentional ingestion of ~200 mL of glufosinate-ammonium (GLA) (13.5%) containing herbicide in an attempted suicide. On examination, the patient presented an acute confusional state. The remaining general and neurological examinations were normal. Arterial blood gas determination showed a hypoxaemic respiratory failure. A gastric lavage followed by the administration of activated charcoal was performed. Brain CT scan was unremarkable. Later, in the intermediate care unit, the patient complained of headache and presented an acute anterograde memory impairment (he could not remember the clinical episode and was unable to retain new memories, but he could recall past events). A 1.5 T brain MRI showed a bilateral hyperintensity and swelling on T2/FLAIR affecting all the hippocampal formation, also extending to the uncus and parahippocampal gyrus, with no restricted diffusion, suggesting vasogenic oedema (figure 1A–D). Cerebrospinal fluid analyses were normal, including the anti-NMDA receptor antibody, other neuron-specific autoantibodies targeting intracellular and plasma membrane antigens, and the herpes simplex virus PCR. The patient was discharged 2 months later. At that moment, his memory impairment was still present but was slowly improving.

Figure 1.

(A) 3D FLAIR, axial reformat parallel to the main hippocampal axis. Bilateral high signal intensity of all the hippocampal formation (head, body and tail) also extends to the uncus. (B) High signal intensity of the adjacent parahippocampal gyrus (arrow). No restricted diffusion (C) or enhancement after gadolinium intravenous administration (D). (E) Schematic representation of a glutamatergic synapse with postsynaptic ionotropic receptor channels. NMDA- N-Methyl-D-aspartate, AMPA -α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid.

GLA, a phosphinic acid derivative of glutamate, is the active component in commercial broad-spectrum herbicides used worldwide.¹ Acute human GLA poisoning may cause various neurological complications depending on the dose ingested.^2–7 A memory deficit, especially selective anterograde amnesia, is one of the possible clinical manifestations.^2–4 Glufosinate is a structural analogue of the neurotransmitter glutamate and may interact with its receptors (figure 1E).^{1 8 9} The NMDA receptor is one of three distinct subtypes of ionotropic receptor channels that are sensitive to the endogenous excitatory amino acid, L-glutamate.^{10 11} The neurons in the hippocampus, which plays a crucial role in learning and memory, function via glutamate receptors.^{12 13} Therefore, hippocampal neurons appear to be susceptible to excitotoxicity by overstimulation of NMDA receptors.^{9 11 14} Focal and nearly symmetrical hippocampal involvement in brain MRI is the imagological translation of this biochemical mechanism. Although cytotoxic oedema affecting the hippocampus has been reported in these cases, GLA may also cause vascular autoregulatory dysfunction, resulting in vasogenic oedema in the hippocampus, as in our case.^{2 5}

The main differential diagnoses related to this imagological pattern were ruled out, namely an autoimmune limbic encephalitis (bilateral involvement of mesial temporal lobes is common since it acts through the same neurotoxic pathway with antibodies against NMDA receptors, but frequently asymmetrical); a herpes simplex virus encephalitis (may have similar findings, often asymmetrical and possibly complicated by haemorrhagic lesions) and an ischaemic stroke in the posterior cerebral arterial territory (isolated hippocampal stroke with no involvement of other structures is rare and should demonstrate restricted diffusion). Indeed, a bilateral symmetrical hippocampal lesion presenting as an acute/subacute anterograde amnesia should raise suspicion for toxic aetiology and must be considered in the differential diagnosis in the presence of a recent history of drug ingestion.

Learning points.

• Acute glufosinate-ammonium intoxication may induce different neurological symptoms depending on the dose ingested.

• The NMDA-type glutamate receptor seems to be the target for glufosinate-ammonium, justifying its predilection for the hippocampus.

• Anterograde amnesia with symmetrical hyperintense hippocampal lesions in brain MRI should raise suspicion for toxic aetiology in the appropriate setting.

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