During the 24 months follow-up we observed a progressive reduction of extrapyramidal signs and the neurological picture finally stabilized to spastic diplegia. Improvement on neuromotor and language skills was also observed. At 24 months of age, he regained head control and he acquired the ability to pronounce single words. At 31 months he was able to stand and maintain sitting position with support and at 43 months he sat without support, he pronounced 2–3 words sentences. Startle reactions, irritability and sleep disturbances progressively disappeared, niaprazine was stopped at 40 months of age. Control MRI, performed at the time of treatment initiation, revealed a spontaneous reduction of T2 white matter hyperintensity with no longer signs of brain atrophy; it was repeated at 31 and 43 months showing progressive normalization of the neuroradiological picture (Fig. 1) without appearance of cerebral calcification even on last CT performed at 31 months of age. Electroencephalographic registration (EEG) revealed a progressive reduction of diffuse centro-occipital delta waves initially evidenced.
Progressive clinical improvement was confirmed on standardized evaluation including Griffiths-III neurodevelopmental scale (Green et al. 2020), Gross Motor Function Measure 88 (Palisano et al. 2000), Functional Classification System Scales (EDACS, CFCS, MACS, GMFCS) (Paulson and Vargus-Adams 2017) and AGS severity score (Adang et al. 2020b) (Fig. 2).
Knowing that AGS usually behaves as a biphasic disease with an initially active phase followed by a chronic stable one which can lead to a misdiagnose of cerebral palsy (Galli et al. 2018), we compared the clinical evolution of our patient to the one expected in children at the same GMFCS initial level. Figure 2c shows that during follow up the GMFM-88 score improved more than expected from children starting from the same GMFCS disability level.
Disease available biomarkers were in line with clinical findings showing progressive normalization: Interferon Score resulted negative starting from 1 month after ruxolitinib initiation. Lumbar puncture was repeated at 12 months from treatment start, IFN alpha and CSF cell count were both normal.
Ruxolitinib was well tolerated, only slight serum CPK fluctuations (max 356 U/l) were detected as also slight hypercholesterolemia (max 252 mg/dl) and hypertriglyceridemia (max 153 mg/dl), both rapidly controlled by dietary management.
Considering the positive response to treatment and recent suggestions about possible neurological regression soon after JAK inhibitors discontinuation, the patient is still on treatment.