Abstract
There are a pressing and unmet need for effective therapies for freezing of gait (FOG) and other neurological gait disorders. Deep brain stimulation (DBS) of a midbrain target known as the pedunculopontine nucleus (PPN) was proposed as a potential treatment based on its postulated involvement in locomotor control as part of the mesencephalic locomotor region (MLR). However, DBS trials fell short of expectations, leading many clinicians to abandon this strategy. Here, we discuss the potential reasons for this failure and review recent clinical data along with preclinical optogenetics evidence to argue that another nearby nucleus, the cuneiform nucleus (CnF), may be a superior target.
Highlights
Gait disturbances present in many neurological diseases and injuries, including Parkinson’s disease (PD), stroke, and spinal cord injuries
Few treatment options exist, making research in this field imperative. In this Perspective article, we review the preclinical developments that led to clinical trials for deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN), discuss potential reasons why these trials have not been successful, and present new research supporting our view that the nearby cuneiform nucleus (CnF) may be a more efficacious target
More than 50 years after the discovery of the mesencephalic locomotor region (MLR), and 15 years after the first-in-man reports of DBS of the PPN, there remains a conspicuous disconnect between basic science and clinical investigations into this midbrain region
Summary
Gait disturbances present in many neurological diseases and injuries, including Parkinson’s disease (PD), stroke, and spinal cord injuries. Both Caggiano et al (2018) and Josset et al (2018) show that activation of glutamatergic CnF neurons is sufficient to initiate locomotion at short latencies; the two studies differ on the role of PPN glutamatergic neurons.
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