Cerebral Amyloid Angiopathy with Cortical Subarachnoid Hemorrhage as a Mimic for Transient Ischemic Attack: A Case Report

Context: Given its cerebral amyloid angiopathy, subarachnoid hemorrhage might represent transient focal neurological episodes erroneously diagnosed as transient ischemic attacks. The earliest neuroimaging findings in emergency room brain computed tomography indicating subarachnoid hemorrhage in these patients might be very subtle and missed by the clinician. Case Presentation: An 80-year-old man referred with transient focal neurological episodes, suggestive of transient ischemic attacks. In general, except for some cognitive dysfunctions, no remarkable point was noticed in his neurological examination. Non-enhanced brain-computer tomography and magnetic resonance imaging revealed evidence indicating slight convexity subarachnoid hemorrhage at the left frontal cortical region. Conclusions: The transient focal neurological episodes uncommonly represent intracranial hemorrhage. Nevertheless, this clinical representation might occur in patients with subarachnoid hemorrhage due to cerebral amyloid angiopathy. In such cases, the neuroimaging findings play a major role in the differential diagnosis. The misdiagnosis of transient ischemic attacks in these cases might lead to the consumption of antiplatelet drugs and end in catastrophic hemorrhage and life-threatening complications. Close attention to patients' clinical findings and judicious use of further neuroimaging studies would help clinicians to avoid making such mistakes.

Effects of optogenetic stimulation of basal forebrain parvalbumin neurons on Alzheimer’s disease pathology

Neuronal activity can modify Alzheimer’s disease pathology. Overexcitation of neurons can facilitate disease progression whereas the induction of cortical gamma oscillations can reduce amyloid load and improve cognitive functions in mouse models. Although previous studies have induced cortical gamma oscillations by either optogenetic activation of cortical parvalbumin-positive (PV+) neurons or sensory stimuli, it is still unclear whether other approaches to induce gamma oscillations can also be beneficial. Here we show that optogenetic activation of PV+ neurons in the basal forebrain (BF) increases amyloid burden, rather than reducing it. We applied 40 Hz optical stimulation in the BF by expressing channelrhodopsin-2 (ChR2) in PV+ neurons of 5xFAD mice. After 1-h induction of cortical gamma oscillations over three days, we observed the increase in the concentration of amyloid-β42 in the frontal cortical region, but not amyloid-β40. Amyloid plaques were accumulated more in the medial prefrontal cortex and the septal nuclei, both of which are targets of BF PV+ neurons. These results suggest that beneficial effects of cortical gamma oscillations on Alzheimer’s disease pathology can depend on the induction mechanisms of cortical gamma oscillations.