Acute Amnestic Syndrome and Ischemic Stroke

Abstract

Purpose of Review

Stroke is an uncommon cause of amnesia. We describe in detail 3 cases of anterograde amnesia and confabulation secondary to acute ischemic stroke and review the available literature.

Recent Findings

In our case series, all 3 patients presented with anterograde amnesia and 2 of 3 copresented with prominent confabulation. These symptoms were recognized in delayed fashion, and no patients received IV tissue plasminogen activator (tPA). Although stroke infarct topology was variable, all 3 patients had infarction of the fornix. Long-term follow-up was obtained in 2 of 3 patients: both had persistent memory impairment and were no longer functionally independent.

Summary

Acute onset anterograde amnesia and confabulation may uncommonly represent acute ischemic stroke. Delays in this diagnosis typically exclude patients from emergent stroke treatment or timely diagnostic stroke evaluation. Clinicians should maintain a high degree of suspicion for ischemic stroke in this setting, especially in patients with comorbid vascular risk factors. Memory impairment secondary to ischemic stroke can produce considerable long-term disability.

Acute onset amnesia represents a diagnostic challenge with a wide differential diagnosis including metabolic, infectious, neurologic, psychiatric, and iatrogenic causes.^1,2 Neurologically, acute onset amnesia may represent transient global amnesia, seizure, encephalopathy, or less commonly, stroke. Although uncommon, infarction has been reported as a cause of acute onset memory loss, especially when localized to the fornix.³ These case reports are primarily derived from iatrogenic complications of anterior communicating artery aneurysm treatment. We report 3 noniatrogenic cases, all of whom presented with amnesia and lack of insight into their deficits resulting in delayed diagnosis. We review their clinical presentation, underlying neuroanatomy, and vascular blood supply.

Case 1

A 61-year-old male patient with a medical history of diabetes mellitus type II (DMII), atrial fibrillation, hypertension (HTN), hyperlipidemia (HL), and tobacco use disorder was noted to be confused by bystanders and brought to the emergency department. On examination, the patient had no insight into his medical condition and no reliable history could be obtained because of confabulation. The patient's National Institutes of Health Stroke Scale (NIHSS) was 2 for incorrect answers to the level of consciousness questions: he did not know the month and reported that he was 40 years old. The patient was also disoriented to year and place. He stated that he was currently living with his wife and children despite being separated. He had impaired delayed recall of verbal and visual memory; his backward digit span was 2. Calculations were accurate but slow, and he had difficulty following multiple-step commands. Ideomotor apraxia and right-left confusion was present. The remainder of his neurologic examination was unremarkable.

His noncontrast head CT was unrevealing. His brain MRI subsequently revealed ischemic stroke of the fornix, genu of corpus callosum, left caudate nucleus, and right anterior frontal lobe. Magnetic resonance angiography (MRA) demonstrated the absence of the right A1 and A2 segments of the anterior cerebral artery (ACA; figure 1). He was not treated with IV tissue plasminogen activator (tPA) because the symptom onset time and was unknown and the diagnosis in the ED was delayed.

Figure 1. Case 1 Neuroimaging.

Row 1: Diffusion-weighted imaging demonstrating infarction of left caudate head (blue arrow), genu of corpus callosum (red arrow), fornix (arrowhead), and right anterior cerebral artery (ACA) stroke (yellow arrows). Row 2: Magnetic resonance angiography showing occlusion of the right A2 segment of the ACA. MRA = magnetic resonance angiography.

His stroke evaluation revealed total cholesterol of 138, low-density lipoprotein (LDL) of 93, high-density lipoprotein (HDL) of 21, and HgA1c of 8.1. His electrocardiogram (EKG) showed atrial fibrillation. Transesophageal echocardiography demonstrated an ejection fraction (EF) of 55%–60%, an enlarged left atrium, normal left ventricular wall motion, and no patent foramen ovale. Given these findings and lack of proximal atherosclerotic disease on MRA, he was diagnosed with cardioembolic stroke secondary to atrial fibrillation. He was started on warfarin, atorvastatin 40 mg, amlodipine 5 mg, and insulin. Owing to his lack of insight and safety concerns, the patient was discharged to a transitional care unit. At his follow-up visit 10 months later, he had ongoing confusion and lack of insight into his medical condition. He had been unable to return to work or independent functional status.

Case 2

A 56-year-old man with a medical history of lacunar stroke, DMII, HL, HTN, and tobacco use disorder was referred to the emergency department for evaluation of new onset confusion. His wife reported that his short-term memory was impaired and that he had been repeating the same stories and questions to his family for the past few days. As an example, she described him frantically looking for a lost coffee cup, but shortly thereafter having no recollection of the event. On examination, his NIHSS was 1 because of his inability to name the month correctly. He was also not oriented to the year, but knew the place. He recalled 0 of 3 words after 5 minutes and could not recall events that happened earlier while in the emergency department. He had no insight into his memory loss. His remote memory was intact, and his speech was fluent. The remainder of his neurologic examination was unremarkable.

On arrival, he was notably hypertensive to 212/115, and his blood glucose was 399. His hypergylcemia and elevated blood pressure were treated; however, his deficits persisted. A brain MRI was obtained and demonstrated an acute infarct within the ventral medial right thalamus and fornix (figure 2). Chronic microvascular ischemic disease was also noted. MRA of the head and neck showed no hemodynamically significant stenosis, aneurysm, or evidence of dissection. Tissue plasminogen activator was not given because of delayed presentation.

Figure 2. Case 2 Neuroimaging.

Restricted diffusion consistent with acute infarcts within the anteromedial right thalamus and fornix.

His stroke evaluation revealed total cholesterol of 178, LDL of 110, HDL of 33, and HgA1c of 12.9. EKG and telemetry demonstrated normal sinus rhythm. Echocardiography showed EF of 60%–65%, grade I diastolic dysfunction, normal left atrial size, and left ventricular wall motion, with patent foramen ovale. Lower extremity ultrasound was negative for deep vein thrombosis. The patient was started on aspirin 325, atorvastatin 40 mg, and glargine insulin 13 units every evening. He was discharged home. He relocated before his stroke clinic appointment and was lost to medical follow-up.

Case 3

A 71-year-old woman with a past medical history of HTN, HL, thyroid disease, and coronary artery disease presented with confusion, disorientation, and confabulation. The family reported that she had seemed fatigued and “not herself” since the evening before admission. At midnight, the patient was found preparing and eating a salad, unaware of the time of day. In addition, she also stated that she was waiting for her mother, who was deceased. Her family encouraged her to go to bed, but she continued to have memory difficulty the following morning.

On examination, her NIHSS was 1 for not knowing the month. She was awake and alert but oriented only to person. She was able to state that she was in the hospital but not aware which one. She was unable to spell the word “world” backward. Short-term memory was impaired. Her MRI demonstrated acute bilateral frontal infarcts in the distribution of the anterior cerebral arteries. Her MRA was notable for bilateral ACA occlusion without proximal atherosclerosis (figure 3).

Figure 3. Case 3 Neuroimaging.

(A and B) Diffusion-weighted imaging demonstrating recent infarcts adjacent to the frontal horns of the lateral ventricular system including the bilateral caudate heads and adjacent white matter, portions of the left posterior frontal lobe, and fornix. (C and D) Diffusion-weighted imaging demonstrating additional punctate infarcts in the right anterior cerebral artery (ACA) territory. (E) Magnetic resonance angiography 3D reconstruction showing occlusion of bilateral ACAs.

Her stroke evaluation revealed total cholesterol of 147, LDL of 72, HDL of 55, and HgA1c of 6.0. Her EKG showed sinus bradycardia with a heart rate of 55. Her echocardiogram was notable only for severe biatrial enlargement without any other noted abnormalities including patent foramen ovale. She was felt to have embolic stroke of undetermined source with a concern for underlying cardioembolism. She was discharged on Coumadin empirically with a 30-day cardiac event monitor. She was transitioned to aspirin after her event monitor was unrevealing.

At her 3-month follow-up appointment, she had slight improvement in her memory impairment, which primarily manifested as poor short-term recall of day-to-day events and reduced recall of autobiographical information. She was, however, able to perform some complex activities of daily living such as paying bills. At times, she acknowledged her memory deficit but seemed indifferent to the significance. She required assistance from family and was no longer functionally independent.

Discussion

We describe 3 patients presenting with acute onset amnesia secondary to ischemic stroke. These cases highlight the challenge of treating acute ischemic stroke in this clinical setting. Despite having debilitating memory loss, none of our patients received IV tPA due to delayed presentation as a result of the patients' and families' lack of insight into their symptoms. Furthermore, had these patients presented emergently, it remains unclear whether a timely stroke diagnosis would have enabled thrombolytic treatment.

Although our patients exhibited varying stroke topology, infarction of the fornix was consistent among all 3 patients. We hypothesize that fornix infarction may be the underlying unifying lesion producing the amnestic syndrome we observed. Similar clinical presentations of amnestic syndrome secondary to fornix infarction are a well-described complication of anterior communicating artery aneurysm repair. In these case reports, patients were noted postprocedurally to have anterograde amnesia often accompanied by confabulation resembling Korsakoff syndrome.^4,5 Temporal confabulation with disorientation to time was especially prominent,^6–8 which was also evident in our case series.

The fornix lies in the center of the hippocampal-diencephalic limbic circuit, where it functions as a conduit for consolidating short-term memory into long-term memory.^7,9 Therefore, injury to this structure leads to anterograde amnesia, affecting the formation of new episodic memories despite maintaining intact long-term memory. Similarly, transient global amnesia, which also produces characteristic anterograde amnesia, is associated with hippocampal lesions within this same circuit.¹⁰ Tractography has demonstrated decreased fiber density of the fornix in an amnestic patient with isolated acute fornix infarction. Six months later, the patient had both major improvement in memory and increased fiber density,⁷ suggesting that injury and recovery of the fiber tracts may be essential to encoding new memory.

The vascular blood supply to the fornix is typically supplied by the subcallosal artery, the dominant branch of anterior communicating artery. Owing to its characteristic “S”-shaped course, infarction of the subcallosal artery produces a sagittally elongated infarction along the medial brain.¹¹ In a minority of patients, the fornix is instead supplied by a single median artery of the corpus callosum.¹² Our second case exhibited concomitant infarction of the anteromedial thalamus. This suggests that the culprit vessel may have been the tuberothalamic artery (a.k.a. polar artery), which originates from the posterior communicating artery.¹³ A single previous case report of fornix infarction also implicated the posterior circulation.¹⁴

In contrast to the existing literature regarding fornix infarction, 2 of our 3 cases had presumed embolic etiology rather than microangiopathy.⁶ This is consistent with studies noting that the callosal arteries are uniquely resistant to microangiopathy,¹⁵ and the primary etiology of ACA territory infarction is cardioembolic.¹⁶ Therefore, it may be important to look for underlying sources of embolic stroke in patients with fornix infarction.¹⁷ Finally, it is notable that all patients in our case series had multiple cardiovascular risk factors, including HTN and HL (3 of 3), DMII (2 of 3), and atrial fibrillation without anticoagulation (1 of 3). Although acute amnestic syndromes are uncommonly caused by stroke, a high degree of suspicion should be maintained in patients with known stroke risk factors.

We report 3 cases of acute ischemic stroke causing amnestic syndrome and confabulation. All cases had underlying fornix infarction. Although nonspecific, it is important that physicians recognize that this presentation may represent an acute ischemic stroke resulting in considerable long-term disability. Prompt recognition and treatment of acute ischemic stroke in this setting may facilitate treatment with thrombolysis and a timely, directed evaluation for secondary stroke prevention.

Appendix. Authors

Study Funding

No targeted funding reported.

Disclosure

The authors report no disclosures relevant to the manuscript. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.