In February 2016, MDPH requested that neurologists, radiologists (including neuroradiologists), and emergency department physicians report any similar cases for medical record review. For the purposes of the review, a case was defined as a patient evaluated in Massachusetts since January 1, 2012 with 1) new onset amnesia in the absence of evidence to support a readily apparent cause, and 2) changes consistent with acute and complete ischemia of both hippocampi on MRI at initial assessment. To investigate each report, the authors (including a board-certified neurologist) reviewed available clinical documentation and diagnostic testing. After preliminary case review, demographic, behavioral, and clinical data, including information related to substance use, were abstracted for analysis from records of patients who met the case definition.

Including the four initial cases, medical records of 25 patients, dating back to 2008, were reviewed after the February 2016 request by MDPH for case reporting. Medical testing was not uniform among all patients, because each patient underwent variable and extensive testing based on clinical context and the assessment of their health care provider. Fourteen (56 percent) patients met the case definition (see Table 1). Among these 14, a total of 11 were identified retrospectively, including two in 2012, five in 2014, and four in 2015. Three were identified prospectively in 2016 after the MDPH request, the most recent in late July 2016. None of the reports of patients with onset before 2012 met the clinical case definition.

TABLE 1. Selected characteristics of 14 patients with sudden-onset amnesia and complete hippocampal ischemia of unclear etiology — Massachusetts, June 2012–July 2016

* One patient had oxycodone/acetaminophen prescribed.
^† Four patients had a benzodiazepine prescribed.
^§ Patient had butalbital/acetaminophen/caffeine prescribed.

All 14 patients had been evaluated at hospitals in eastern Massachusetts. One was a resident of southeastern New Hampshire and another was visiting from the state of Washington. Patient age ranged from 19 to 52 years (mean and median = 35 years). Nine patients were unconscious at the time they came to medical attention, five of whom required endotracheal intubation. After regaining consciousness, all nine were noted to be amnestic. Among the other five patients, family members, friends, or acquaintances observed the emergence of severe memory loss after limited time apart and brought them to the emergency department for further assessment. In addition to striking anterograde amnesia, deficits of orientation, attention, and executive function were variously noted. These deficits were reported to have improved over time, with resolution of memory loss in one patient at five months, but persisting in two patients with follow-up of more than one year (see Table 2). For 13 patients, MRI of the head was performed within five days of initial evaluation, and at eight days in the 14th patient. In addition to bilateral hippocampal ischemia (Figure), nine patients also exhibited ischemic changes in one or more, often asymmetric extra-hippocampal regions, primarily in the subcortical and posterior areas (see Table 2). Follow-up MRI in one patient, at five weeks, demonstrated complete resolution of the initial abnormalities; in two other patients, at 13 and 22 months after onset, MRI revealed residual, bilateral hippocampal volume loss.