Review Question - QID 217722

This patient developed transient anterograde amnesia (does not remember location or time, and is unable to recall new information) following a trigger (likely a Valsalva maneuver during an attempted bowel movement) and has otherwise no other focal neurological deficits most likely developed transient global amnesia. Of the available answer choices, this condition could most likely be due to central venous congestion affecting hippocampal venous drainage.

Transient global amnesia is an acute, episodic inability to generate new memories that, by definition, resolves within 24 hours. The pathophysiology of the condition is not entirely clear but likely involves the hippocampus given its key role in memory formation. One popular hypothesis revolves around venous congestion, whereby events that cause central venous congestion (such as known triggers like sympathetic activation from emotion, diving reflex, or Valsalva maneuver). Older adults between 50 and 80 have a higher prevalence of transient global amnesia. Potential risk factors may include migraine, hypertension, and hyperlipidemia – their association is, however, contested in different studies. Regarding presentation, the primary feature of the condition is sudden anterograde amnesia with variable levels of retrograde amnesia. Semantic and procedural memories as well as other cognitive features (e.g., speech, language comprehension, etc.) are not normally significantly affected. Except for the gap in the amnesic episode, patients’ symptoms usually completely resolve. Most episodes last longer than 1 hour with a mean duration of 6 hours. The condition is a clinical diagnosis and requires that there is no preceding head trauma, no loss of personal identity, and no other focal neurologic signs. Transient global amnesia usually does not recur and no specific treatment is necessary.

Spiegel et al. review another etiology for transient global amnesia. Regarding its pathophysiology, another hypothesis is arterial ischemia, driven by the similarity between transient global amnesia and transient ischemic attacks (TIA). Although both conditions occur in a similar age demographic, patients with transient global amnesia have been shown to have significantly lower levels of embolic heart disease, hypertension, atherosclerosis, and diabetes compared to TIA patients. Furthermore, episodes of TIA are usually much shorter (<1 hour) compared to transient global amnesia.

Incorrect Answers:
Answer 1: Abnormal synchrony of hippocampal neuron firing is consistent with seizure. A seizure can involve a specific region (focal) or can cause global impairment (generalized). In focal seizures, consciousness may be spared and symptoms depend on the affected area. In generalized seizures, consciousness is not spared and more severe symptoms (such as tonic-clonic contractions and jerking) usually manifest. For etiology, seizures are either provoked (e.g., metabolic abnormalities, toxins, etc.) or unprovoked (primary neurological disorder like neurofibromatosis). In patients with epilepsy, there is a rare condition called transient epileptic amnesia that has a similar presentation to transient global amnesia, but the episodes are usually much shorter (less than 1 hour).

Answer 2: Buildup of amyloid plaques and neurofibrillary tangles in the hippocampus is consistent with Alzheimer disease. It is a chronic neurodegenerative disease that leads to cognitive and behavioral decline that affects normal daily activities. The pathophysiology is unclear, but histology reveals extracellular amyloid plaques and intraneuronal neurofibrillary tangles. Its clinical characteristics include not only an inability to remember new information but also impaired declarative memory (e.g., specific events in the past). Although the patient has anterograde amnesia, it was acute in onset and resolved after 6 hours.

Answer 4: Ischemia injury to CA1 hippocampal neurons is consistent with stroke, which occurs when the blood supply to a brain region is cut off. Strokes are often either embolic (clots that form outside the brain vasculature and travel to the brain) or thrombotic (clots that form within the brain vasculature). As CA1 neurons are particularly vulnerable to ischemia, anterograde amnesia is not an uncommon symptom. However, this patient had complete recovery of his amnestic symptoms, which would not be seen in untreated stroke.

Answer 5: Temporal lobe mass effect secondary to venous bleeding is consistent with a subdural hemorrhage, which develops when the rupture of bridging veins leaks blood into the subdural space. Subdural hematomas are commonly secondary to head trauma such as assault or falls in the elderly. In acute cases, patients would have signs of increased intracranial pressure such as headache, nausea, vomiting, and/or cranial nerve palsies. For this patient, he did not have any evidence of trauma on the exam or any signs of increased intracranial pressure. Furthermore, his symptoms resolved without intervention.

Bullet Summary:
Characterized by acute onset anterograde amnesia without other focal neurological signs that resolve within 24 hours, transient global amnesia is likely due to hippocampal insult, such as impaired venous drainage.