The motor complications that arise several years after initiating treatment for Parkinson’s disease (PD) are, in part, attributed to abnormal neuroplasticity of the corticostriatal circuits resulting from fluctuating synaptic dopamine levels [1]. In the advanced stages of PD, continuous dopaminergic stimulation (CDS) has been demonstrated to alleviate motor complications, and one approach to achieving CDS is through levodopa-carbidopa intestinal gel (LCIG) therapy [1]. Recently, we encountered a case in which motor complications ceased after short-term LCIG therapy using a nasogastric tube, and this positive effect persisted for six months post-intervention.

A 76-year-old female, diagnosed with PD according to the International Parkinson and Movement Disorder Society diagnostic criteria, had initially presented with a resting tremor in her left lower limb at the age of 65 years. Her initial treatment included levodopa/carbidopa 100 mg/10 mg taken three times a day and trihexyphenidyl 2 mg twice a day. At the age of 67, she visited our department with a resting tremor in her left hand, limb rigidity, and bradykinesia. Subsequent examinations, including 123I-metaiodobenzylguanidine scintigraphy and dopamine transporter scintigraphy, revealed reduced cardiac uptake and striatal uptake, respectively. Due to the risk of motor complications, the treatment was switched to pramipexole (3 mg). A wearing-off phenomenon occurred at age 71, followed by dyskinesia at age 73. Despite oral medication adjustments, persistent motor complications led to the initiation of LCIG therapy. At this point, the patient was on levodopa/carbidopa 850 mg/85 mg/day (divided into six doses), pramipexole 3 mg, opicapone 25 mg (tablet), zonisamide 25 mg, and rasagiline 1 mg, totaling a levodopa equivalent daily dose (LEDD) of 1,530 mg. In the offstate (approximately 30% of the day), she required assistance in walking due to rigidity, bradykinesia, strong camptocormia, and postural instability. In the on-stage (the remaining 70% of the day), she could walk independently, though she experienced dyskinesia throughout her body. Her Mini-Mental State Examination score was 28 points, indicating preserved cortical function. Oral medications were discontinued, and LCIG therapy using a nasogastric tube was initiated. Initially, 8 mL of LCIG was administered in the morning (equivalent to 160 mg of levodopa), followed by a continuous infusion of 3.4 mL/h (68 mg/h) for 16 h (LEDD 1,248 mg), eliminating off periods but exacerbating dyskinesia. Subsequently, on the second day, the continuous dose was reduced to 3.0 mL/h (60 mg/h), and the patient’s dyskinesia completely resolved (LEDD 1,120 mg). LCIG therapy was initiated on the seventh day, and on the following day, all oral medications, except rasagiline and zonisamide, were resumed (LEDD 1,430 mg). The patient remained in an on-state throughout the day, and no off or dyskinetic episodes were observed for six months (Figure 1).

In summary, a noteworthy aspect of our case is the sustained symptom improvement for a certain period even after reverting to oral treatment following short-term LCIG therapy. Several reports suggest that short-term interventions in PD patients lead to symptom improvement with sustained effects. One such intervention is a “Drug Holiday (DH),” involving the temporary withdrawal of PD medications, with benefits persisting in some patients for more than six months to one year or longer after cessation [2]. DH restores reduced dopamine receptor sensitivity by markedly lowering dopamine levels [2]. In contrast, LCIG generates a more stable increase in striatal dopamine levels and decreased dopamine receptor binding (availability) [3]. Considering these differences, we speculate that dopamine receptor availability in the striatum is less related to the maintenance of improvements in motor complications obtained with short-term intervention.

Therefore, we focused on the corticostriatal circuit downstream of the striatal postsynaptic dopamine receptor. Pulsatile stimulation of postsynaptic receptors due to fluctuating synaptic dopamine levels leads to abnormal cascade changes in gene and protein synthesis, resulting in morphological abnormalities and abnormal neuroplasticity in the corticostriatal circuit, which in turn contribute to motor complications [1,4]. It has been reported that LCIG can normalize inappropriate changes in cortical neuroplasticity [5]. Additionally, several studies have shown that short-term repetitive transcranial magnetic stimulation (rTMS), which directly modulates cortical neuroplasticity, ameliorates motor complications over a certain period [6]. Among these studies, Shirota et al. [7] demonstrated the longest-lasting benefits by stimulating the supplementary motor area in 36 PD patients with an average age of 68 years, a disease duration of 8.5 years, using low-frequency (1 Hz) stimulation for 17 minutes, and observing motor improvement for 20 weeks. Based on this evidence, we speculate that the alteration in cortical neuroplasticity played a role in the sustained efficacy in our patient, in whom the cortical function was presumably preserved.

Another reported short-term intervention is intravenous infusion of levodopa [8]. Mouradian et al. [8] observed 12 PD patients with motor complications, an average age of 62 years, and a disease duration of 14 years who switched from oral administration to intravenous infusion of levodopa around the clock for 7–12 days. Motor complications were reduced; however, these effects deteriorated only 6 days after the patients returned to oral treatment. Inadequate patient information in this report prevents a full understanding of why fluctuations in dopamine levels, stabilized by intravenous infusion, did not lead to long-term effects, as seen in DH or our case.

Our case study reinforces the theory that abnormal neuroplasticity in corticostriatal circuits contributes to motor complications and suggests the potential impact of short-term CDS on the aforementioned abnormal cascade changes induced by pulsatile dopaminergic stimulation. Regrettably, our study lacked an assessment of blood/striatal dopamine levels and cortical neuroplasticity, as has been reported by Kolmančič et al. [5]. Not all patients receiving short-term interventions, such as DH, rTMS, and LCIG, show symptomatic improvement [2,6], which emphasizes the need for research to elucidate factors influencing the duration of short-term intervention effects.

In conclusion, our case suggests the potential of short-term LCIG therapy using a nasogastric tube as a therapeutic strategy for improving motor complications in patients with PD.

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