Introduction
Parkinson’s disease (PD) is the second most common neurodegenerative
disorder, affecting millions of people worldwide and significantly
impacting their quality of life [1]. The disease is characterized by
the progressive loss of dopaminergic neurons in the substantia nigra,
leading to the hallmark motor symptoms of bradykinesia, rigidity, and
tremor [2]. In addition to motor impairments, PD patients often
experience various non-motor symptoms, such as cognitive decline, sleep
disorders, and autonomic dysfunction [3].
Current treatment options for PD primarily focus on pharmacological
interventions, including dopamine replacement therapy with levodopa,
dopamine agonists, and other medications that modulate neurotransmitter
levels [4]. While these treatments can provide symptomatic relief,
they are often associated with side effects and long-term complications,
such as motor fluctuations and dyskinesias [5]. Deep brain
stimulation (DBS) has emerged as an effective surgical treatment for
advanced PD, particularly for patients who experience inadequate symptom
control or intolerable side effects from medications [6]. However,
DBS also has limitations, including invasive surgery, potential adverse
effects, and a narrow patient selection criteria [7].
Recent advancements in neuromodulation technologies have opened new
avenues for the development of more targeted and less invasive
treatments for PD. These emerging techniques, such as next-generation
cranial nerve stimulation and other novel neuromodulation approaches,
hold the potential to address the limitations of current therapies and
improve patient outcomes [8]. The focus of this review is to provide
a comprehensive overview of the latest advancements in cranial nerve
stimulation and neuromodulation techniques for PD treatment, their
clinical applications, and the evidence supporting their safety and
efficacy.
In recent years, several new devices and stimulation protocols have been
developed to modulate the activity of specific cranial nerves and brain
regions involved in PD pathophysiology [9]. Non-invasive techniques,
such as transcranial magnetic stimulation (TMS) and transcranial direct
current stimulation (tDCS), have shown promise in modulating cortical
excitability and improving motor and non-motor symptoms in PD patients
[10, 11]. Furthermore, minimally invasive approaches, like vagus
nerve stimulation (VNS) and trigeminal nerve stimulation (TNS), have
demonstrated potential benefits in both preclinical and clinical
studies, with fewer side effects compared to traditional treatments
[12, 13].
This review aims to critically evaluate the current state of the art in
cranial nerve stimulation and neuromodulation techniques for PD
treatment, by discussing the underlying principles, devices, and
protocols, as well as the clinical evidence supporting their use. We
also analyze the advantages and limitations of these innovative
approaches, their potential to transform PD management, and the
challenges that need to be addressed in future research and clinical
applications. By shedding light on this emerging field, we hope to
contribute to the ongoing efforts to develop more effective and
better-tolerated treatment options for PD, ultimately improving the
quality of life for millions of patients affected by this debilitating
disorder.