We present a systematic evaluation and optimization of a complex bio-medical signal processing application on the BrainWave prototype system, targeted towards ambulatory EEG monitoring within a tiny power budget of 1 mW. The considered BrainWave processor is completely programmable, while maintaining energy-efficiency by means of a Coarse-Grained Reconfigurable Array (CGRA). This is demonstrated through the mapping and evaluation of a state-of-the-art non-convulsive epileptic seizure detection algorithm, while ensuring real-time operation and seizure detection accuracy. Exploiting the CGRA leads to an energy reduction of 73.1%, compared to a highly tuned software implementation (SW-only). A total of 9 complex kernels were benchmarked on the CGRA, resulting in an average 4.7 × speedup and average 4.4 × energy savings over highly tuned SW-only implementations. The BrainWave processor is implemented in 28-nm FDSOI technology with 80 kB of Foundry-provided SRAM. By exploiting near-threshold computing for the logic and voltage-stacking to minimize on-chip voltage-conversion overhead, additional 15.2% and 19.5% energy savings are obtained, respectively. At the Minimum-Energy-Point (MEP) (223 μW, 8 MHz) we report a measured state-of-the-art 90.6% system conversion efficiency, while executing the epileptic seizure detection in real-time.