Restless Legs Syndrome (RLS), also known as Willis–Ekbom disease, is a common neurological sensorimotor disorder characterized by an irresistible urge to move the legs, typically accompanied by uncomfortable sensations such as tingling, burning, or creeping feelings [1]. These symptoms predominantly occur during periods of rest or inactivity, particularly in the evening or at night, and are temporarily relieved by movement. The circadian pattern of symptom exacerbation often leads to significant sleep disturbances, impairing overall quality of life [2].

Restless Legs Syndrome (RLS) is a common neurological disorder with a variable global prevalence [3]. Worldwide, its prevalence is estimated to range between approximately 3% and 7%, affecting hundreds of millions of individuals. Higher prevalence rates have been reported in Western countries, while relatively lower but still significant rates are observed in Asian populations [4]. In Asia, the prevalence generally ranges from 1% to 8%, likely influenced by genetic, environmental, and diagnostic differences. In Pakistan, studies have reported notably higher prevalence rates, with some estimates reaching up to 23.6% in certain populations . More recent regional data from Quetta indicate a prevalence of approximately 12.1%, highlighting the growing recognition of RLS in local populations . Overall, RLS remains underdiagnosed despite its substantial burden on sleep and quality of life [5] . Despite the growing recognition of RLS worldwide, there is limited published evidence describing its clinical characteristics, sleep-related consequences, and treatment patterns in Pakistan, particularly in Balochistan. Local epidemiological data are essential to improve early diagnosis, optimize management strategies, and guide future healthcare planning.

These findings are consistent with current hypotheses implicating dopaminergic dysfunction and altered iron metabolism in the pathophysiology of RLS. Although iron status was not assessed in the present study, previous research has identified iron deficiency and altered brain iron homeostasis as important contributors to RLS pathogenesis [6]. The pathophysiology of RLS is not fully understood; however, growing evidence implicates dysfunction in central dopaminergic pathways and impaired iron homeostasis within the brain. Iron deficiency, particularly in the substantia nigra, is believed to disrupt dopamine synthesis and signaling, thereby contributing to symptom manifestation [7]. Genetic factors also play a significant role, with several susceptibility loci identified through genome-wide association studies [8]. RLS can be classified as either primary (idiopathic), often with a familial predisposition, or secondary, associated with underlying conditions such as chronic kidney disease, pregnancy, peripheral neuropathy, and iron deficiency anemia. The clinical diagnosis is primarily based on established criteria, including an urge to move the legs, worsening symptoms during rest, relief with movement, and circadian variation [9].

Management strategies for RLS involve both non-pharmacological and pharmacological approaches. Lifestyle modifications, including sleep hygiene and reduction of caffeine intake, are recommended for mild cases. Pharmacological treatment typically includes dopaminergic agents, alpha-2-delta calcium channel ligands, and iron supplementation when deficiency is present. However, long-term use of certain medications may lead to complications such as augmentation, necessitating careful therapeutic planning [7, 10]. RLS is a multifactorial neurological disorder with significant clinical and social implications [11]. Therefore, the present study aimed to evaluate the demographic characteristics, clinical manifestations, sleep disturbances, lifestyle factors, treatment practices, and factors associated with disease burden among patients diagnosed with RLS attending a tertiary care hospital in Quetta, Pakistan.

Study Design and Setting

A retrospective observational record-based study was conducted at the Department of Neurology, Bolan Medical Complex Hospital (BMC), Quetta, Pakistan, a tertiary care referral hospital serving patients from Balochistan and neighboring regions. The study aimed to evaluate the demographic characteristics, clinical features, sleep disturbances, lifestyle factors, and treatment patterns among patients diagnosed with Restless Legs Syndrome (RLS).

A total of 519 eligible patient records were included in the analysis. All records contained complete information for the predefined study variables, and no missing data were identified for the variables included in the final analysis. The dataset comprised 24 variables covering demographic characteristics, clinical symptoms, sleep-related problems, lifestyle habits, family history, diagnostic evaluation, treatment practices, and patient-reported treatment outcomes.

Study Duration

Medical records of patients attending the Neurology Department between January 2025 and December 2025 were reviewed retrospectively.

Study Population

The study population consisted of both inpatient and outpatient records of patients diagnosed with Restless Legs Syndrome (RLS) at the Department of Neurology, Bolan Medical Complex Hospital, Quetta, during the study period.

Inclusion Criteria

Patient records were included if they met all of the following criteria:

• Confirmed diagnosis of Restless Legs Syndrome based on the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria.
• Attendance at the Neurology Department between January 2025 and December 2025.
• Complete clinical records containing all variables required for the study.

Exclusion Criteria

Records were excluded if they:

• Did not meet the IRLSSG diagnostic criteria for Restless Legs Syndrome.
• Contained incomplete demographic or clinical information.
• Represented duplicate patient records or follow-up entries with insufficient information for analysis.

Sample Size

A census sampling approach was adopted. All eligible patient records meeting the inclusion criteria during the study period were included in the analysis, resulting in a final sample of 519 patients.

Data Collection

Data were extracted retrospectively from hospital medical records using a structured data extraction form. Information collected included:

• Demographic characteristics (age, gender, marital status, and occupation);
• clinical characteristics (symptom frequency, duration, anatomical distribution, sensation type, aggravating and relieving factors);
• sleep-related variables (sleep duration and degree of sleep disturbance);
• lifestyle factors (physical activity, smoking, alcohol use, caffeine intake, dietary modifications, and family history);
• diagnostic investigations;
• treatment modalities; and
• patient-reported treatment effectiveness.

Patient identifiers were removed before data analysis to ensure confidentiality.

Ethical Considerations

Ethical approval for the study was obtained from the Ethics Committee of Bolan Medical Complex Hospital, Quetta. As this was a retrospective record-based study utilizing anonymized hospital records, the requirement for informed consent was waived. All patient information was handled confidentially, and data were analyzed anonymously in accordance with institutional ethical guidelines.

Statistical Analysis

Data were entered and analyzed using IBM SPSS Statistics version 20.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were used to summarize the study variables and are presented as frequencies, percentages, means, and standard deviations, where appropriate.

Associations between categorical variables were examined using the Chi-square test of independence, and the strength of significant associations was assessed using Cramér's V. Relationships between ordinal variables were evaluated using Spearman's rank-order correlation coefficient (ρ). All statistical tests were two-tailed, and a p-value < 0.05 was considered statistically significant.

Demographic Characteristics

Table 2.1 summarizes the demographic profile of the 519 RLS patients. The cohort was predominantly female (52.4%), reflecting the known higher prevalence of RLS in women. The largest age group was patients above 60 years (28.1%), consistent with the age-dependent nature of RLS. Most patients were married (61.3%) and employed (56.8%).

Table 2.1. Demographic Characteristics of RLS Patients (N=519)

Clinical Symptom Profile

Table 2.2 presents the full clinical symptom profile. Symptoms occurred most frequently at evening (40.1%) and were of moderate duration (10–30 min; 43.4%). Both legs were the primary site of discomfort (59.3%), with tingling (33.3%) and aching (29.3%) as the predominant sensations. Walking was the most effective relief strategy (35.6%), consistent with the cardinal RLS diagnostic criterion of symptom relief with movement.

Table 2.2. Clinical Symptom Characteristics (N=519)

Impact on Sleep and Daily Functioning

The majority of patients (83.6%) reported that RLS interfered with their sleep to some degree: mild (43.4%), moderate (13.5%), or severe (26.8%). More than half (53.4%) slept less than 6 hours per night  a clinically important finding given the recommended 7–9 hours for adults. RLS impacted daily activities for 69.7% of patients to at least some degree, and 35.3% reported increased psychological stress as the predominant associated experience.

Table 2.3. Impact on Sleep and Daily Life (N=519)

Lifestyle and Worsening Factors

Nearly half of patients (49.9%,) reported being physically inactive. Smoking was identified as the most common worsening factor (38.2%), followed by stress (30.3%) and alcohol consumption (15.4%). Regarding dietary modifications, 35.1% were reducing caffeine intake, 27.9% were consuming iron-rich foods, and 32.9% were unsure about dietary effects. Family history of RLS was present in 56.6% of patients.

Table 2.4. Lifestyle Factors and Family History (N=519)

Treatment and Diagnosis

The majority (80.5%) had received a formal RLS diagnosis. Among treatment approaches, home remedies were most commonly used (31.4%), followed by lifestyle changes (25.0%) and prescription medications (20.4%). Regarding medications, antidepressants were the most frequently prescribed class (31.4%). Medical investigation included blood tests (27.9%), neurological tests (24.7%), and sleep studies (8.3%). Treatment was rated 'somewhat effective' by 38.2% of patients, with only 3.9% reporting it to be 'very effective.'

Table 2.5. Diagnosis, Treatment, and Effectiveness (N=519)

INFERENTIAL STATISTICS

Chi-Square Tests of Independence

Table 3.1 presents results of 16 chi-square analyses examining associations between key clinical and demographic variables. Twelve associations were statistically significant at p < 0.001. The largest effect size was observed between Treatment Type and Treatment Effectiveness (Cramér's V = 0.640), indicating a strong and clinically meaningful relationship. Family History vs RLS Sleep Interference (V = 0.388) and Age Group vs RLS Sleep Interference (V = 0.376) were also notable. Three variables  Age vs Formal Diagnosis, Gender vs Diagnosis, and Marital Status vs RLS  did not reach statistical significance.

Table 3.1. Chi-Square Tests of Independence (N=519)

Note: *** p < 0.001; ** p < 0.01; * p < 0.05; ns = not significant. Cramér's V interpretation: 0.10–0.29 = small effect; 0.30–0.49 = moderate effect; ≥ 0.50 = large effect.

Spearman Rank-Order Correlations

Table 3.2 presents Spearman rank-order correlations among six ordinal variables. RLS Sleep Interference showed significant negative correlations with Hours of Sleep (ρ = −0.322, p < 0.001) confirming that greater RLS severity is associated with reduced sleep duration and with Treatment Effectiveness (ρ = −0.285, p < 0.001). Age was positively correlated with Symptom Frequency (ρ = 0.319, p < 0.001), indicating older patients tend to have more frequent symptoms. Daily Life Impact was negatively associated with both Sleep Hours (ρ = −0.204) and Treatment Effectiveness (ρ = −0.236).

Table 3.2. Spearman Rank-Order Correlations Among Ordinal Variables (N=519)

Note: *** p < 0.001; * p < 0.05; ns = not significant. ρ = Spearman's rho correlation coefficient.

The present study provides important insight into the clinical burden, symptom characteristics, lifestyle associations, and treatment experiences of patients with Restless Legs Syndrome (RLS) in Quetta, Pakistan. The findings demonstrate that RLS is not merely a minor sensory complaint but a significant neurological disorder associated with insomnia, impaired daily functioning, psychological stress, and reduced treatment satisfaction. Importantly, this study highlights several overlooked aspects of RLS that may contribute to its underdiagnosis and suboptimal management in this healthcare setting.

Among the most important findings of the present study was that the participants reported very frequent manifestation of their symptoms, with more than 42.2%, (n = 219)  experiencing symptoms often and a significant portion even experiencing them daily. The dominance of evening and night-time occurrence of the symptoms clearly corresponds to the classical circadian rhythmicity of RLS and confirms the reliability of the diagnosis among participants in the study. Also, the fact that symptoms were alleviated by movement in 87.5% of the participants is in accordance with another cardinal sign of RLS and highlights the neurological origin of the condition. Moreover, the walking activity turned out to be the most common form of movement alleviating the symptoms, which suggests that patients use behavioral strategies to deal with sensory discomfort.

Another important aspect related to the clinical symptom profile of the participants is their diffuse and disabling nature. First of all, almost everyone had the involvement of both legs 59.3 % (n = 308)  in the disease, while tingling 33.3 % (n=173) and aching 29.3% (n=152) sensations were most common symptoms. All of those symptoms coincide with results from previous research showing the role of abnormal sensory perception and dopaminergic dysfunction in generation of unpleasant sensations in the limbs and corresponding motor urge [12].

One of the major findings from the current research pertained to the significant influence that RLS has on sleep and everyday activities. Overall, 83.6% of patients reported some degree of sleep interference (n=430), with almost a quarter of those interviewed experiencing severe sleep disturbance. What is more alarming is that more than half of the respondents slept for less than six hours a day 37.6% (n=195), which is a worrying statistic taking into account the known link between long-term sleep deprivation and various diseases such as cardiovascular disorders, problems with cognition and emotion regulation, as well as overall poor quality of life. A negative association between RLS sleep interference and sleep duration provides another example of evidence proving the assumption that RLS severity leads to insufficient sleep [1].

 However, RLS had repercussions on the individual beyond sleep issues, affecting their psychosocial well-being and functioning in an extremely negative manner. Almost three-quarters 34.1 % (n=177) of the subjects complained about the impact of the condition on their everyday life, whereas the increased stress was noted as the most common associated feeling. Such results imply that the impact of RLS reaches far beyond the discomfort in terms of sleep problems, possibly influencing mental health deterioration, lower productivity, and inability to function effectively socially. Furthermore, the association of sleep disruption and its impact on everyday life points at the possibility of the deterioration of daytime functioning due to nighttime difficulties. One of the more noteworthy findings that was highlighted in this particular research study was the link that exists between certain lifestyle habits and symptoms of RLS. It was found that nearly fifty percent of patients 56.6 % (n=294) were completely sedentary, and that there was an observed link between activity and symptoms, as well as between activity and sleep disruption. From this information, it is clear that one of the reasons why symptoms may worsen could be due to physical inactivity 49.9 % (n=259), which could cause poor circulation. Conversely, exercise may represent a beneficial adjunctive strategy, as it may improve sleep quality and dopaminergic function.

The importance of smoking being the most frequently reported exacerbating factor is another clinically important finding in the study. Exposure to nicotine 38.2 % (n=198) has earlier been linked to dopamine dysregulation, vascular changes, and disruption in sleep patterns, which have the potential to exacerbate RLS symptoms. Smoking was frequently reported as an aggravating factor and may be associated with increased symptom severity among individuals with RLS. Other factors like stress emerged as an important aggravating factor, pointing to a more complex interplay among neurological symptoms, mental health issues, and disturbed sleep.

Among the factors identified in this study, one of the most alarming was the correlation between efficacy of the treatment received and patients' perception of its effectiveness, More than half of the participants reported a family history of RLS (56.6%, n=294). Significant associations were observed between family history, symptom frequency, and sleep interference. These findings support previous evidence suggesting a genetic contribution to RLS susceptibility and heredity in cases of RLS, which was established by various studies conducted internationally as well. Thus, the high presence of the familial component among local participants may suggest that genetic susceptibility plays a crucial role in this community.

In addition, the prevalence of self-management of RLS with home remedies 31.4 % (n=163) and changes in lifestyle 25.1 % (n=130) rather than pharmacological therapy, indicates potential shortcomings in the delivery of specialized neurological treatment and patient education.

It is noteworthy that antidepressants 31.4 % (n = 163) were the most common type of prescribed drug. Although antidepressants are often prescribed to patients with mood disorders, due to their serotonergic effects on dopaminergic certain antidepressants may aggravate RLS symptoms in susceptible individuals. This issue should be considered when prescribing pharmacological treatment. Moreover, the low frequency of sleep studies and neurological examinations in the diagnosis of RLS can indicate the diagnostic capabilities of local health-care facilities. The use of inferential statistical analysis also makes the study results highly scientifically relevant. Chi-square tests have shown statistically significant relations between certain demographic, lifestyle, and clinical characteristics. The observed effect sizes suggest that some associations may have practical significance in addition to statistical significance. Thus, such high effect sizes in the association between treatment method and its effectiveness, as well as between physical exercise, family history, age, and sleep disturbance, point to the interplay of different factors in the development of RLS.

The current research sheds light on RLS as an important and yet neglected neurological condition with major public health implications among the population of the region in question. The considerable burden of sleep disorders, psychological distress, functional impairments, and suboptimal effectiveness of treatment seen in this patient group indicates that numerous individuals suffer from their chronic complaints in spite of receiving medical care. This implies the critical need to pay more attention to clinical awareness, timely detection, consistent diagnosis, and proper management of RLS patients in Pakistan. Improving their health and well-being would require focusing on lifestyle changes, sleep evaluations, patient education, and evidence-based treatment options.

Nevertheless, some weaknesses can be outlined in relation to this research. First of all, the retrospective and cross-sectional design of the study makes it impossible to establish a cause-and-effect relationship between variables analyzed. Furthermore, the fact that the data were gathered retrospectively, based both on records and patient reports, may lead to various forms of biases, including recall and reporting biases. At the same time, the use of only one tertiary care center as the source of data makes it hard to generalize the results.

Strengths of the Study

This study has several strengths.

• Large sample size: The study included 519 patients diagnosed with Restless Legs Syndrome (RLS), providing sufficient data to comprehensively describe the demographic and clinical characteristics of patients attending a tertiary care hospital.
• Real-world clinical data: The use of hospital records reflects routine clinical practice, making the findings relevant to everyday patient management and healthcare planning.
• Comprehensive clinical assessment: Multiple aspects of RLS were evaluated, including demographic characteristics, symptom profile, sleep disturbance, daily functional impairment, lifestyle factors, family history, diagnostic evaluation, treatment practices, and treatment effectiveness, providing a holistic overview of the disease burden.
• Use of standardized diagnostic criteria: Patients were identified using the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria, improving the validity and consistency of case identification.
• Appropriate statistical analysis: Both descriptive and inferential statistical methods, including Chi-square tests, Cramér's V, and Spearman's rank correlation, were used to explore clinically relevant associations between patient characteristics and disease outcomes.
• Regional contribution: To the best of our knowledge, this is among the few studies describing the clinical characteristics and management of RLS in patients from Balochistan, providing valuable baseline evidence for clinicians, researchers, and policymakers.

Limitations of the Study

Despite its strengths, the study has several limitations.

• Single-center design: The study was conducted at a single tertiary care hospital; therefore, the findings may not be generalizable to the wider population of Pakistan or to primary and secondary healthcare settings.
• Retrospective design: The use of existing medical records limited the availability of some clinical variables and prevented verification of missing or inaccurate information.
• Hospital-based sample: Only patients who sought medical care at a tertiary referral hospital were included, introducing potential selection bias and limiting the ability to represent individuals with undiagnosed or milder disease in the community.
• Lack of objective laboratory and sleep assessments: Important variables such as serum ferritin levels, iron status, polysomnography findings, and neurophysiological investigations were not consistently available and therefore could not be evaluated.
• Absence of validated severity assessment: Disease severity was not measured using a standardized instrument such as the International Restless Legs Syndrome Rating Scale (IRLS), limiting assessment of symptom severity and treatment response.
• Causal relationships cannot be established: Owing to the observational retrospective design, the significant associations identified should not be interpreted as causal relationships.
• Potential information bias: Some patient-reported variables, including lifestyle habits and perceived treatment effectiveness, may be subject to documentation inaccuracies or reporting bias.

This study demonstrates that Restless Legs Syndrome (RLS) is associated with substantial sleep disturbance, impaired daily functioning, and reduced treatment effectiveness among patients attending a tertiary care hospital in Quetta, Pakistan. Most patients experienced frequent symptoms that were predominantly worse during the evening, with a high proportion reporting significant sleep disruption and functional impairment. Family history, physical inactivity, and smoking were significantly associated with greater symptom burden, highlighting the potential influence of genetic and modifiable lifestyle factors on disease expression.  Although most patients had received a formal diagnosis, treatment outcomes were generally suboptimal, with many reporting only partial symptom relief. These findings underscore the need for improved clinical recognition, comprehensive patient assessment, individualized treatment strategies, and regular follow-up to optimize disease management and improve patient quality of life. Given the considerable impact of RLS on sleep and daily functioning, increasing awareness among healthcare professionals and the public, promoting healthy lifestyle modifications, and implementing evidence-based management strategies are essential. Further multicenter prospective studies incorporating standardized severity assessment tools and objective clinical investigations are recommended to better characterize RLS and guide effective management strategies in Pakistan.

CLINICAL RECOMMENDATIONS

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