Introduction: Huntington's Disease as progressive neurological disorders associated with motor, behavioral, and cognitive impairment poses a therapeutic challenge in case of limited responsiveness to established therapeutics. Pallidal deep brain stimulation and neurorestorative strategies (brain grafts) scoping to modulate fronto-striatal circuits have gained increased recognition for the treatment of refractory Huntington's disease (HD).
Areas covered: A review (2000-2022) was performed in PubMed, Embase, and Cochrane Library covering clinical trials conceptualized to determine the efficacy and safety of invasive, stereotactic-guided deep-brain stimulation and intracranial brain-graft injection targeting the globus pallidus and adjunct structures (striatum).
Expert opinion: Stereotactic brain-grafting strategies were performed in few HD patients with inconsistent findings and mild-to-moderate clinical responsiveness with a recently published large, randomized-controlled trial (NCT00190450) yielding negative results. We identified 19 in-human DBS trials (uncontrolled) targeting the globus pallidus internus/externus along with randomized-controlled trial pending report (NCT02535884). We did not detect any significant changes in the UHDRS total score after restorative injections, while in contrast, the use of deep-brain stimulation resulted in a significant reduction of chorea. GPi-DBS should be considered in cases where selective chorea is present. However, both invasive therapies remain experimental and are not ready for the implementation in clinical use.
Keywords: Huntington´s disease; brain grafts; chorea; deep-brain stimulation; dystonia; efficacy; fronto-striatal circuits; globus pallidus externus/internus; parkinsonism; quality of life; safety; striatum; unified Huntington´s disease rating scale (UHDRS).