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.