Sialorrhea is defined as the chronic and excessive flow of saliva beyond the lip margin, which may substantially impair both social functioning and overall quality of life (QoL) (1, 2). Excessive salivation represents a frequent yet often underestimated complication of several neurological disorders, most notably cerebral palsy (CP), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) (3–6). Reported prevalence in PD varies across studies but frequently exceeds 50%, reflecting differences in disease stage, assessment methods, and populations (7). Rather than resulting from excessive salivary gland secretion (hypersalivation), sialorrhea in PD usually results from impaired oropharyngeal motor control or swallowing dysfunction, leading to inefficient saliva clearance and accumulation in the oral cavity (8–10). Current treatment options include pharmacological agents, often used off-label, as well as conservative non-pharmacological interventions. Systemic drugs, particularly anticholinergic agents, are frequently associated with adverse effects (11, 12). In contrast, intraglandular botulinum neurotoxin type A injections (IncoBoNT/A) exert their effect locally at the site of saliva production, offering a focal and well-tolerated alternative. IncoBoNT/A has been approved for both adult and pediatric patients, representing a valid option or adjunctive therapy (13). Recent clinical trials and subsequent regulatory approvals have confirmed the efficacy of IncoBoNT/A for sialorrhea treatment, validating long-standing clinical observations (14–24). However, botulinum toxin injections are associated with certain limitations and risks, largely due to their invasive nature. The procedure requires specific preparation, operator training, and clinical experience. Ultrasound guidance is generally recommended to improve accuracy and safety (25, 26). However, excessive or improperly targeted injections in the submandibular gland may result in transient but clinically significant dysphagia, particularly in patients with advanced PD (13, 14, 20, 21, 27). Conversely, insufficient dosing may fail to adequately control symptoms. Moreover, the invasive nature of the procedure poses challenges in patients with CP, where tolerance and acceptance are often limited. Given these limitations, alternative noninvasive approaches warrant investigation.

Low-energy extracorporeal shock wave therapy (ESWT) has recently emerged as a noninvasive neurological intervention primarily employed to reduce spasticity and hypertonia in conditions such as stroke and CP (28–30). Preclinical and clinical studies suggest that ESWT may transiently reduce muscle hypertonia through mechanisms involving decreased acetylcholine release at the neuromuscular junction, enhanced nitric oxide (NO) release, and anti-inflammatory effects (31, 32).

The aim of this study was to investigate the effects of low-energy, noninvasive ESWT applied to the salivary glands in patients with advanced PD or atypical parkinsonian syndromes and persistent sialorrhea, with the objective of assessing its potential anticholinergic-like action and evaluating its efficacy in reducing hypersalivation.

Baseline demographic characteristics and clinical features of patients are shown in Table 1.

According to item 2 of section II of the UPDRS, 10 of the 12 patients reported severe salivation requiring constant use of tissues or handkerchiefs, whereas the remaining two experienced salivation while awake but generally did not require them.

No statistically significant correlations were found between clinical variables and DSFS, NHRS, and SCS-PD scores (data not shown).

For DSFS, repeated measures GLM revealed a significant effect of Time, F(4, 44) = 6.40, p < 0.001, partial η² = 0.368. In particular, a statistically significant difference was observed between T0 and T1 and T2 (Table 2 and Figure 3), with a reduction of the score at week 1 and 4.

Also for NHRS, repeated measures GLM showed a significant effect of Time, F(2.54, 27.92) = 6.16, p = 0.004, partial η² = 0.359. In particular, a statistically significant difference was observed between T0 and T1 (Table 2 and Figure 4), with a reduction of the score at week 1.

Finally, also for SCS-PD repeated measures GLM showed a significant effect of Time, F(4, 44) = 7.52, p < 0.001, partial η² = 0.406. In particular, a statistically significant difference was observed between T0 and T1, T2, and T3 (Table 2 and Figure 5), with a long-lasting reduction of the score at week 1, 4, and 8.

A decrease in hypersalivation on the PGI-Change during the first month was reported by 75% (9/12) of patients. Of these, 66.7% (6/9) noted only minimal improvement, whereas the remaining three described themselves as “improved” (2/9) or “much improved” (1/9). The remaining three patients did not report any improvement following the treatment. These results were corroborated by the CGI-Change, indicating that 83.3% (10/12) of patients exhibited some degree of improvement in hypersalivation. Of these, 70% (7/10) were rated as minimally improved and 30% (3/10) as improved, while 16.7% (2/12) showed no change.

Finally, also DIS score showed a statistically significant reduction form baseline to week 4, in particular: T0 = 42.5 (37–71) vs T2-week4 = 38 (28–71), Wilcoxon signed rank test, p = 0.005 (Figure 6).

The main finding of this study is the significant effect of ESWT in reducing sialorrhea in patients with PD and atypical parkinsonian syndromes, as demonstrated by the clinical rating scales. The effect was evident both in terms of clinical improvement and subjective benefit. The improvement was evident as early as 1 week after treatment and persisted up to 4 weeks when assessed with the DSFS, and even longer, up to 8 weeks, according to the SCS-PD. Importantly, ESWT was well tolerated, and no adverse events or treatment-related discomfort were observed. No patients reported discomfort during stimulation, nor adverse effects such as pain, excessive dryness, or dysphagia. ESWT did not interfere with normal salivation or with saliva production during eating, digestion, or emotional stimuli.

Salivation is a complex autonomically regulated process that represents the initial step in digestion. The major salivary glands (parotid, submandibular, and sublingual) produce between 1 and 1.5 liters of saliva daily. The parotid glands receive parasympathetic innervation via preganglionic neurons in the inferior salivatory nucleus, with project through the glossopharyngeal nerve and lesser petrosal nerve to the otic ganglion (33). In PD, subcortical and brainstem structures involved in autonomic and motor control are affected early, leading to systemic and oropharyngeal bradykinesia (34). This results in impaired swallowing, inefficient clearance of saliva, and accumulation of secretions in the oral cavity. Historically, sialorrhea in PD has been attributed to excessive salivary production secondary to autonomic dysfunction. However, more recent studies demonstrate that saliva output is actually reduced in PD compared to healthy controls (9, 35). Therefore, sialorrhea in PD is most likely due to impaired swallowing, secondary to oropharyngeal bradykinesia, and the inability to clear secretions, leading to excessive pooling of saliva rather than hypersalivation (10). This distinction has therapeutic relevance, as treatments that further suppress salivary secretion, such as BoNT/A injections, may inadvertently worsen swallowing function in vulnerable patients. BoNT/A injections are currently considered the gold standard for sialorrhea management, with robust supporting evidence from clinical trials and case series (14–24). BoNT/A acts by selectively binding to peripheral cholinergic nerve terminals, where it is internalized and inhibits acetylcholine release at the neuroglandular junction, in a dose-dependent but reversible manner (36, 37). Despite proven efficacy and relatively favorable safety profile, BoNT/A injections are invasive, require ultrasound guidance, and can occasionally cause transient dysphagia or xerostomia. These limitations can reduce their applicability in patients with advanced PD or atypical parkinsonism, who often have poor tolerance or cooperation. By contrast, ESWT exerts its effect through local modulation of glandular function without directly impairing swallowing dynamics. Its principal advantage lies in its noninvasive, painless, and repeatable nature—particularly valuable in frail patients at risk of dysphagia or swallowing disturbances due to oropharyngeal bradykinesia.

The relatively long-lasting reduction in sialorrhea observed in this study suggests that ESWT could represent a feasible therapeutic option for this disabling symptom, particularly in patients with advanced PD and atypical parkinsonian syndromes. ESWT has gained increasing application in neurology, particularly in the treatment of spasticity in stroke and CP patients (28, 38). The mechanisms underlying the effects of ESWT on salivation remain speculative. Experimental evidence suggests that low-energy shock waves can modulate cholinergic neurotransmission through a transient reduction in acetylcholine release at the neuromuscular junction. Additionally, ESWT may enhance local nitric oxide (NO) production, improve microcirculation, and exert anti-inflammatory effects at the tissue level (31, 32, 39–41). These effects may collectively downregulate salivary gland activity, producing an anticholinergic-like modulation without systemic exposure and side effects. In this regard, the action of ESWT may parallel the functional mechanisms observed in its use for spasticity reduction (29, 30, 42–44).

This preliminary study represents an initial step in exploring an innovative, palliative, and noninvasive treatment for sialorrhea in advanced PD. Its noninvasive, painless, and repeatable nature enhances patient adherence and tolerability. Although the magnitude of improvement observed in our cohort was modest compared with BoNT/A trials, the absence of adverse effects and the favorable safety profile position ESWT as a promising adjunctive or alternative treatment for sialorrhea, especially in patients at high risk of aspiration or intolerance to invasive procedures. Beyond potential symptomatic relief, reducing drooling may also mitigate secondary complications such as perioral skin maceration, aspiration, and social embarrassment, while improving patients’ social confidence and QoL.

However, several limitations should be acknowledged. The small sample size and open-label, uncontrolled design limit statistical power and generalizibility. Objective assessments of salivary flow, such as sialometry or salivary gland scintigraphy, were not performed. Moreover, potential placebo effects cannot be excluded. These limitations warrant confirmation through larger, multicenter, randomized controlled studies.

In conclusion, our findings provide preliminary evidence that low-energy ESWT applied to the major salivary glands is a safe, well-tolerated, and potentially effective noninvasive intervention for sialorrhea in PD and related disorders. ESWT may exert local modulatory effects on glandular activity without compromising swallowing function, making it particularly suitable for fragile or cognitively impaired patients.

In our protocol, ultrasound imaging was employed to guide the treatment application, ensuring accurate targeting of the salivary glands. Although not intended for morphological assessment, ultrasonographic monitoring contributed to the precision and safety of ESWT delivery. Therefore, we suggest that integrating a pre- and post-treatment ultrasonographic evaluation could represent a valuable procedural adjunct for future studies, providing further insight into potential tissue-level effects of ESWT.

Future randomized, double-blind, sham-controlled studies with extended follow-up are needed to confirm efficacy, define optimal treatment parameters, and elucidate the underlying physiological mechanisms. If validated, ESWT could represent an innovative, accessible, and patient-friendly addition to the therapeutic options for the management of sialorrhea in neurodegenerative conditions.