Diagnostic challenges in restless abdomen syndrome: A case report

Abstract

BACKGROUND

Restless abdomen is a rare phenotypic variant of restless legs syndrome (RLS), characterized by visceral discomfort and an urge to move localized to the abdominal region. Due to its atypical presentation, it is frequently misdiagnosed as a primary psychiatric or functional gastrointestinal disorder, leading to ineffective management.

CASE SUMMARY

We report the case of a 55-year-old female presenting with significant visceral discomfort and an irresistible urge to move localized to the abdomen, accompanied by severe anxiety and chronic insomnia. Initial treatment with standard antidepressant and hypnotic regimens for a suspected primary anxiety disorder proved ineffective. A comprehensive workup excluded underlying gastrointestinal pathologies. Diagnostic clarification was achieved via polysomnography, which revealed a significantly elevated periodic limb movement index (37.7 events/hour), providing objective neurophysiological support for an RLS diagnosis. Following the confirmation of an abdominal variant of RLS, monotherapy with pramipexole (0.25 mg/day) was initiated. The therapeutic response was rapid and robust: Within one week, abdominal restlessness resolved, and sleep quality normalized. Clinical remission was corroborated by marked reductions in the Hamilton Anxiety Rating Scale (from 20 to 3) and Hamilton Depression Rating Scale (from 10 to 3) scores.

CONCLUSION

Restless abdomen syndrome is easily misdiagnosed, making meticulous history taking, iron screening, and polysomnography paramount.

Key Words: Restless abdomen syndrome; Restless legs syndrome; Comorbidity of anxiety and insomnia; Dopaminergic therapy; Case report

Core Tip: Restless abdomen syndrome is an under-recognized variant of restless legs syndrome characterized by abdominal discomfort worsening at rest. This report describes a patient previously misdiagnosed with anxiety-induced insomnia. A novel finding was isolated hypotransferrinemia despite normal ferritin, suggesting a specific deficit in blood-brain barrier iron transport. The patient achieved complete remission with the dopamine agonist pramipexole. This report underscores the diagnostic value of the circadian symptom pattern and suggests that transferrin levels may offer mechanistic insights into restless legs syndrome variants, alerting clinicians to avoid misdiagnosing this treatable condition as a psychiatric disorder.

INTRODUCTION

Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a sleep-related movement disorder characterized by discomfort in the legs and an overwhelming urge to move them. Symptoms typically occur or intensify in the evening or at night, are exacerbated during periods of rest or inactivity, and are alleviated by movement[1]. Variants of RLS often involve areas other than the legs, such as the chest, back, abdomen, face, and bladder, with similar cases already reported[2,3]. Restless abdomen, characterized by restlessness in the abdomen, is an uncommon disorder with a prevalence of approximately 6.7% among RLS patients[4]. However, the isolated incidence remains unknown, with limited systematic analysis of its association with anxiety and insomnia, as existing literature consists mainly of case reports[5-8]. Patients with RLS and its variants are often misdiagnosed, particularly when psychiatric symptoms coexist. We report this case to systematically explore the mechanisms of restless abdomen comorbid with anxiety-insomnia and propose a multimodal treatment approach, providing new insights into clinical recognition and intervention.

CASE PRESENTATION

Chief complaints

A 55-year-old female presented with paroxysmal nocturnal abdominal discomfort and severe sleep maintenance insomnia persisting for over one year.

History of present illness

The patient reported a core symptom characterized by deep, indescribable sensations of “throbbing” or “vague pain” localized to the abdomen. Notably, these sensations were accompanied by an irresistible urge to move or massage the affected area. The patient explicitly denied any involvement of the lower extremities. Her symptoms exhibited a classic circadian pattern: Emerging exclusively during nocturnal rest or while attempting to sleep, promptly relieved by activities such as walking or abdominal massage, and recurring rapidly upon resuming rest. This led to severe sleep maintenance insomnia, with 3 to 5 awakenings reported per night. Her abdominal discomfort was not prominent during the daytime. Over the one-year course, her abdominal symptoms were closely intertwined with significant nocturnal anxiety, including palpitations, tension, and persistent apprehension about harboring a serious, undiagnosed illness. These psychiatric symptoms coincided almost exclusively with the nocturnal onset of visceral sensations.

Her diagnostic journey prior to our clinic was extensive. Comprehensive evaluations at multiple general hospitals, including gastrointestinal endoscopy, contrast-enhanced abdominal computed tomography, and computed tomography enterography, revealed no organic abnormalities. Due to the tight temporal coupling between her emotional and somatic symptoms and negative organic workup, she was initially misdiagnosed with an “anxiety disorder”. Consequently, she was treated with a systematic pharmacotherapy regimen of escitalopram (20 mg/day), zopiclone (7.5 mg/night), and lorazepam (1 mg/night), which provided only transient and partial relief before losing efficacy.

History of past illness

The patient’s medical history was unremarkable except for a transcervical polyp resection performed six months prior to presentation.

Personal and family history

She had no history of smoking or alcohol consumption. There was no reported family history of RLS or other movement disorders.

Physical examination

Neurological and gastrointestinal examinations were universally normal.

Laboratory examinations

Routine laboratory investigations, including vitamin B12 and folate, were within normal limits. A complete blood count revealed a hemoglobin level of 138 g/L and a red blood cell count of 4.49 × 10¹²/L. Notably, while her serum ferritin (164.6 ng/mL; reference value 10-291.0 ng/mL) and whole-blood iron (8 mmol/L; reference value 7.27-9.85 mmol/L) levels were preserved, isolated hypotransferrinemia was identified (1.83 g/L; reference value 2-3.6 g/L).

Imaging examinations

Radiological imaging (cranial magnetic resonance imaging), electroencephalogram, and electrocardiogram were unremarkable. Psychological assessments at baseline showed a Hamilton Depression Rating Scale score of 10, a Hamilton Anxiety Rating Scale score of 20, and a Pittsburgh Sleep Quality Index score of 18 (Figure 1). Polysomnography (PSG) revealed a periodic limb movement index (PLMI) of 37.7 events/hour (Figure 2 and Table 1).

Figure 1 Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and Pittsburgh Sleep Quality Index scores before and after treatment. HAMA: Hamilton Anxiety Rating Scale; HAMD: Hamilton Depression Rating Scale; PSQI: Pittsburgh Sleep Quality Index.

Figure 2 Periodic limb movements during sleep of the patient before treatment. The arrows indicate leg movements. RIP: Respiratory inductance plethysmography; ECG: Electrocardiogram.

Table 1 Polysomnography findings before and after treatment.

Parameters	Before treatment	After treatment
Total sleep time (minutes)	335	460
Sleep efficiency (%)	75.2	95.2
Sleep latency period (minutes)	55	10
N1 stage (%)	7.3	5.6
N2 stage (%)	69.8	55.8
N3 stage (%)	10.2	23.5
R stage (%)	12.7	15.1
Apnea-hypopnea index (events/hour)	8.8	8.5
Periodic limb movement index (events/hour)	37.7	8.5

FINAL DIAGNOSIS

According to the diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG), and supported by evidence of elevated PLMI on PSG, she was diagnosed with restless abdomen syndrome (RLS variant).

TREATMENT

As an RLS variant was suspected, the previous antidepressants were discontinued. Treatment with the dopamine agonist pramipexole was initiated at 0.125 mg/day. To mitigate potential benzodiazepine withdrawal, the concurrent lorazepam was initially tapered to 0.5 mg/day. To address mild residual discomfort observed after the first week, the pramipexole dosage was titrated to 0.25 mg/day. Lorazepam was subsequently tapered and successfully discontinued during outpatient follow-up.

OUTCOME AND FOLLOW-UP

The adjusted regimen yielded rapid symptomatic improvement. Within one week, the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores dropped to 3, and the Pittsburgh Sleep Quality Index normalized to 5. A follow-up PSG at six months demonstrated a significant reduction in PLMI from 37.7 events/hour to 8.5 events/hour (Table 1). During the one-year follow-up period, no symptom recurrence was observed. The patient maintained clinical remission on a stable regimen of pramipexole (0.25 mg at night), necessitating no dosage escalation. Safety monitoring confirmed the absence of dopaminergic adverse events, including augmentation or impulse control disorders. Additionally, a cross-sectional assessment at the one-year endpoint yielded an International Restless Legs Syndrome Rating Scale score of 8, objectively corroborating the patient’s subjective report of satisfactory symptom control and minimal impact on daily life.

DISCUSSION

Diagnostic confirmation of this abdominal variant relied on adhering to the IRLSSG core criteria[1], specifically the pathognomonic circadian pattern and rest-induced exacerbation, despite the atypical localization. A rigorous differential diagnosis was paramount. Organic gastrointestinal pathologies were excluded following imaging and endoscopy. Crucially, the distinction from functional gastrointestinal disorders (e.g., functional dyspepsia and visceral hypersensitivity) was established based on the symptom profile; unlike primary functional gastrointestinal conditions, the patient’s discomfort exhibited a distinct circadian rhythm (predominantly evening/night), exacerbation during rest, and rapid relief with physical activity. Furthermore, the concomitant anxiety and depression were determined to be secondary consequences of the sleep disturbance rather than primary psychiatric etiologies, a conclusion supported by their parallel resolution alongside the abdominal symptoms following the initiation of pramipexole. Neurological mimics such as belly-dancer dyskinesia[9] and propriospinal myoclonus[5] were ruled out by the clinical phenotype, cranial magnetic resonance imaging, and PSG findings. The diagnosis was ultimately solidified by the elevated PLMI index (37.7 events/hour) and the robust response to dopaminergic therapy. Collectively, these findings validate restless abdomen as a distinct phenotypic variant sharing a common dopaminergic pathophysiology with classic RLS[5-7].

While the exact pathogenesis of RLS remains incompletely understood, it is primarily attributed to central dopaminergic dysfunction, brain iron deficiency (BID), and genetic factors. Notably, while this patient did not exhibit overt anemia or low ferritin, an isolated reduction in serum transferrin (1.83 g/L) was observed. Contrary to traditional views focusing on peripheral ferritin stores, recent research has highlighted the pivotal role of iron transport proteins within the neurovascular unit[10,11]. Transferrin serves as the primary vehicle for iron transport across the blood-brain barrier. Hypotransferrinemia may impair the efficiency of iron delivery to the central nervous system, thereby precipitating BID despite preserved peripheral stores[12]. This central iron insufficiency directly impacts RLS pathophysiology via dopaminergic pathways: Iron acts as an obligatory cofactor for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis[12]. Reduced brain iron compromises tyrosine hydroxylase activity, leading to unstable presynaptic dopamine synthesis and a compensatory downregulation of postsynaptic D2 receptor density. Thus, the reduced transferrin likely constituted the rate-limiting step for functional BID in this case, explaining the severe, dopaminergic-responsive symptoms in the absence of systemic anemia. The favorable clinical response to pramipexole aligns with this hypothesis.

To contextualize this rare phenotype, a comparative analysis of restless abdomen cases reported over the past five years was performed (Table 2). This analysis highlights the distinctiveness of the present case in three key domains. First, regarding phenotypic purity, unlike the largest case series, where 70% of patients exhibited concurrent leg involvement[7], our patient presented with a strictly isolated abdominal variant, increasing the diagnostic challenge. Second, in terms of metabolic biomarkers, this case diverges from the classic iron deficiency (low ferritin) profile. The identification of isolated hypotransferrinemia points towards a specific transporter-level dysfunction at the blood-brain barrier rather than systemic store depletion. Finally, concerning diagnostic rigor, the integration of PSG-confirmed PLMI[13] and documented sustained 1-year remission distinguishes this report from cases relying solely on subjective descriptions[14], providing robust evidence for this treatable clinical entity.

Table 2 Summary of reported restless abdomen cases and clinical characteristics (2020-2025).

Ref.	Patient (age/sex)	Core symptoms	Leg involvement?	Key investigative findings (iron and PSG)	Treatment and outcome	Distinctive features
Vijayan et al[14], 2025	1 (23 years, F)	Deep “swirling” sensation in the left upper abdomen, urge to move, and severe insomnia, no family history of RLS	No	Iron: Not reported; PSG: Not performed; Vitamin D3: Low	Pramipexole (0.125 mg/day); complete resolution	Very young onset; diagnosed in a psychiatry setting; lacks objective PSG/iron data
Sun et al[13], 2022	1 (60 years, M)	Unpleasant abdominal sensations begin approximately 30 minutes after lying down, relieved by rubbing, slapping the abdomen, or walking; caused difficulty falling asleep; no mention of family history	No	PSG (video): Documented urge to move abdomen during rest and periodic limb movements of sleep (PLMS); labs: Hemoglobin, iron, ferritin normal; imaging: GI endoscopy and abdominal CT normal; genetic testing: Not performed	Pramipexole (0.25 mg/day); good response over 8 months of treatment	High-quality video evidence of urge to move; classic isolated phenotype with normal iron
Wang et al[7], 2020	10 (mean: 68.8 years, 8 F/2 M)	Sensations: Itching, crawling, numbness, soreness; all showed classic RLS circadian/rest-activity patterns; family history: 1/10 (10%) positive	Yes (7/10); no (2/10); chest (1/10)	Iron: Low in 50% (ferritin < 75 or TSAT < 20%); PSG: PLMS confirmed (in 3 tests); mean IRLS 27.7 (moderate-severe); genetic testing: Not reported	Dopaminergic therapy (pramipexole 0.25 mg/day) alone or combined with gabapentin; positive response in all patients	Largest series; shows isolated abdominal RLS is rare (20%); high prevalence of iron deficiency
This case	1 (55 years, F)	Nocturnal abdominal discomfort, irresistible urge to move, severe anxiety and insomnia; no family history of RLS	No	Iron: Normal ferritin; transferrin: Low (1.83 g/L); PSG: PLMI 37.7 events/hour; imaging: GI endoscopy, abdominal CT and cranial MRI normal; genetic testing: Not performed	Pramipexole (0.25 mg/day); good response over one week; sustained remission (1-year follow-up)	Combines key features: (1) Isolated abdominal phenotype; (2) Objective PSG confirmation; (3) Unique biomarker finding (isolated low transferrin); and (4) Documented long-term efficacy; suggests a potential distinct biochemical correlate

M: Male; F: Female; RLS: Restless legs syndrome; IRLS: International restless legs syndrome study group rating scale; PLMS: Periodic limb movements in sleep; PLMI: Periodic limb movement index; PSG: Polysomnography; CT: Computed tomography; GI: Gastrointestinal; MRI: Magnetic resonance imaging; TSAT: Transferrin saturation.

First-line treatments for RLS include iron replacement, calcium channel α2δ ligands, and dopamine agonists[15,16]. The 2025 American Academy of Sleep Medicine clinical practice guideline recommends iron supplementation for adult RLS patients with serum ferritin levels ≤ 75 ng/mL or transferrin saturation < 20%[17], consistent with the 2018 IRLSSG task force report[18]. In the present case, serum ferritin (164.6 ng/mL) exceeded the treatment threshold, and whole-blood iron was normal. Consequently, iron therapy was not initiated. As the patient’s symptoms proved refractory to the initial regimen of escitalopram, zopiclone, and lorazepam, pramipexole was initiated, resulting in marked symptomatic improvement. This robust response subsequently enabled dose reduction and eventual discontinuation of lorazepam.

Three key clinical implications arise from this case. Firstly, regarding antidepressant necessity in comorbid anxiety: Evidence suggests that mild to moderate depressive symptoms in RLS often resolve following effective symptom control[19,20]. Antidepressants should therefore be reserved for persistent mood disturbances after adequate RLS treatment. The choice of agent is critical; mirtazapine, fluoxetine, and sertraline may exacerbate motor symptoms or Periodic Limb Movements in Sleep (PLMS), whereas trazodone generally does not[21,22]. Secondly, regarding the mechanism of mood improvement: Pramipexole may exert direct antidepressant effects, potentially mediated by D3 receptors in limbic regions[23,24]. Its benefits may thus extend beyond the mere relief of restlessness. Although our observation aligns with studies showing dual improvement[25], the RLS-depression relationship remains complex and warrants further investigation[26]. Finally, regarding lorazepam: This agent did not appear central to managing core symptoms, consistent with previous reports[8]. While benzodiazepines may offer short-term adjunctive benefits for sleep, treatment should be tailored to the individual profile.

This study has several limitations. Firstly, genetic testing (e.g., BTBD9) was not performed as it was not routinely available at our center, and the patient declined additional testing post-remission. Secondly, although PSG provided supportive evidence via PLMI, a key limitation is that we did not include dedicated abdominal surface EMG channels to directly record and quantify the patient’s reported abdominal motor events. This is because abdominal EMG is not a routine part of our center’s PSG protocol. This underscores the need for more phenotype-specific objective measures in future studies.

Future research should prioritize large-scale epidemiological studies and multicenter registries to elucidate the relationship between restless abdomen and classic RLS, including shared genetic foundations. Furthermore, future PSG studies of RLS variants should consider incorporating multi-site surface EMG, including abdominal channels, to objectively capture motor activity beyond the limbs. The development and validation of variant-specific assessment tools, such as adapting the International Restless Legs Syndrome Rating Scale for non-leg regions, would be invaluable for standardizing clinical evaluation.

CONCLUSION

Restless abdomen syndrome is a rare RLS variant prone to misdiagnosis, especially when comorbid with anxiety and depression. A meticulous medical history regarding the symptom circadian rhythm is essential. When indicated, PSG should be utilized to objectively evaluate PLMS; while PLMS criteria are traditionally validated against leg movements, their presence strongly supports an RLS-spectrum diagnosis and aids in differentiation from mimics. Additionally, screening for iron metabolism markers beyond ferritin—specifically transferrin—may offer critical diagnostic clues.

ACKNOWLEDGEMENTS

We express our gratitude to the patient, whose co-operation and consent were essential for the documentation of this case.