Neural plasticity impairment in chronic post-surgical hypoparathyroidism: a cross-sectional and prospective pilot...

Despite adequate conventional therapy, patients with chronic post-surgical hypoparathyroidism (HypoPT) frequently report persistent physical, emotional, and cognitive symptoms that affect quality of life, despite no overt cognitive impairment. The neurophysiological mechanisms underlying these complaints remain unclear.

To assess cortical excitability and plasticity in HypoPT patients using transcranial magnetic stimulation (TMS) and to explore the effects of parathyroid hormone (PTH) therapy on these parameters.

We conducted a cross-sectional study including 32 HypoPT patients on stable conventional treatment without significant cognitive impairment and 16 age-matched healthy controls. In a prospective observational phase, a subgroup of six HypoPT patients (3-palopegteriparatide and 3-teriparatide) was reassessed after 48 months of PTH therapy. All participants underwent TMS evaluation, including motor evoked potentials (MEPs), short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI), and assessment of plasticity using intermittent theta burst stimulation (iTBS). The primary outcome was the change in MEP amplitude after iTBS as an index of cortical plasticity.

MEP changes following iTBS differed significantly between HypoPT patients and controls (-0.02 vs 0.4 mV; P = 0.003; corrected P = 0.042), indicating reduced cortical plasticity in HypoPT. In contrast, HypoPT patients receiving long-term PTH therapy showed a significant increase in MEP amplitude, comparable to healthy controls. No other TMS measures differed significantly.

This pilot study provides preliminary evidence of impaired cortical plasticity in HypoPT in the absence of overt cognitive impairment. Although limited by small sample size, the findings suggest that PTH therapy may modulate cortical plasticity. Further research is needed to clarify the clinical relevance and potential central nervous system effects of PTH in HypoPT.