Anterograde amnesia and hippocampal lesions: is fentanyl the culprit?

January 31, 2018, 1:23 pm

Hippocampus (


An Unusual Amnesic Syndrome Associated With Combined Fentanyl and Cocaine Use. Duru LB et al. Ann Intern Med 30 Jan 2018 [Epub ahead of print]


Last year we reviewed an MMWR report describing 14 cases of anterograde amnesia associated with substance abuse and bilateral ischemia of the hippocampi, as well as an additional paper giving somewhat more detailed clinical information on the initial four cases.

This letter describes an additional case that occurred in West Virginia. A 30-year-old man with a history of heroin use was found at home to be difficult to arouse. When he came to his mental status was abnormal and he seemed to be asking the same questions repeatedly.

At hospital, serum and urine drug screens were positive for cocaine but negative for opiates. CT head showed “bilateral, symmetrical hypodensities in the hippocampus and basal ganglia.” He was diagnosed with anterograde amnesia. Diffusion-weighted MRI imaging showed hyperintensities in the regions of the hippocampi, fornices, mammilary bodies, and globus pallidus.

A urine sample apparently obtained several days after admission was negative for fentanyl but positive for one of its metabolites (norfentanyl.)The remainder of the drug screen was negative (although it is not clear how extensive the tests were.)

In their discussion, the authors cite another somewhat similar case from Virginia. They note that although the syndrome of amnesia and hippocampal lesions has been reported in association with exposure to carbon monoxide as well as cocaine alone, there was no evidence of carbon monoxide toxicity in this case, and only 2 of the 13 patients tested in the MMWR series were positive for cocaine. No patient in that series was tested for fentanyl.

The authors hypothesize that “cocaine and fentanyl together potentiate the underlying mechanism of injury, including the potential for both excitotoxic and hypoxic-ischemic processes.”

A little bit more detail on the case would have been helpful. It is not clear if the patient had respiratory insufficiency, was hypoxic, or received naloxone before he “became more alert.” If this syndrome were just caused by fentanyl — or even fentanyl in combination with cocaine — we probably would have seen many more such cases by now. I suspect that there is still some undetected drug or adulterant that was responsible or contributory. But I agree with the authors’ conclusion that in cases of new-onset unexplained amnesia, specific testing for fentanyl and its metabolites and analogs is warranted.

UPDATE: Undark has a very good discussion of these cases and why this syndrome may be much more important than the small number of patients reported so far would suggest. Recommended reading.

Related posts:

Anterograde amnesia and bilateral hippocampus ischemia: is it caused by substance abuse?

Amnesia and hippocampal ischemia in 4 opiate abusers: a case series


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