Cerebral Amyloid Angiopathy-Related Transient Focal Neurologic Episodes

Abstract

Transient focal neurologic episodes (TFNEs) are brief disturbances in motor, somatosensory, visual, or language functions that can occur in patients with cerebral amyloid angiopathy (CAA) and may be difficult to distinguish from TIAs or other transient neurologic syndromes. They herald a high rate of future lobar intracerebral hemorrhage, making it imperative to differentiate them from TIAs to avoid potentially dangerous use of antithrombotic drugs. Cortical spreading depression or depolarization triggered by acute or chronic superficial brain bleeding, a contributor to brain injury in other neurologic diseases, may be the underlying mechanism. This review discusses diagnosis, pathophysiology, and management of CAA-related TFNEs.

Figure 1. Convexity Sulcal Subarachnoid Hemorrhage (cSAH) and Cortical Superficial Siderosis (cSS)

A 71-year-old woman presented with paresthesias and weakness of the right hand. (A) CT showed acute cSAH in a left frontal sulcus, visible as a linear hypointensity on T2*-weighted gradient-recalled echo (GRE) MRI (B). MRI GRE also showed 3 areas of cSS (arrows, C and D) in sulci without acute cSAH. One year later, the patient had a left parietal lobar intracerebral hemorrhage.

Figure 2. Possible Mechanisms Triggering Spreading Depolarizations

Schematic representation of hypotheses on the origin of spreading cortical depolarizations (CSDs) within a sulcus affected by cerebral amyloid angiopathy (CAA). Convexity subarachnoid hemorrhage (cSAH) and cortical superficial siderosis (cSS) could trigger CSD by releasing chemical factors that affect the brain tissue or pial vasculature. An acute cortical microbleed might also trigger CSD via ischemia (Isch) in the territory of the ruptured artery, via mechanical distortion of brain tissue by expanding microbleed, or by release of depolarizing factors from plasma leakage or hematoma lysis (e.g., potassium [K+] ions or glutamate [Glu]). Once initiated, CSDs propagate in cortical gray matter at a speed of ∼3 mm/min for many centimeters, creating a TFNE.

Figure 3. MRI Diffusion-Weighted Imaging (DWI) in Cerebral Amyloid Angiopathy (CAA)–Related Transient Focal Neurologic Episodes (TFNEs) Compared With Ischemic Stroke

(A–C) From the same patient, disseminated cortical superficial siderosis (cSS) on MRI susceptibility-weighted imaging (A) with a 3 mm focus of bright signal on DWI in the left superior frontal gyrus adjacent to cSS (B, circled) with hypointensity on apparent diffusion coefficient image (C, circled), indicating restricted diffusion. Small (≤10 mm) DWI-positive lesions are often seen in CAA with convexity subarachnoid hemorrhage and TFNEs, usually adjacent to regions of cSS and sometimes multiple. (D–F) DWI-positive lesion patterns seen in ischemic stroke but not CAA include single larger (>10 mm) DWI-positive infarcts (D), multiple DWI-positive infarcts restricted to a vascular perfusion territory (E), or DWI-positive small subcortical infarcts restricted to the territory of a single perforating artery (as in the thalamic recent subcortical infarct seen in F).