A machine learning model to predict the risk of perinatal depression: Psychosocial and sleep-related factors in the Life-ON study cohort.

Perinatal depression (PND) is a common complication of pregnancy associated with serious health consequences for both mothers and their babies. Identifying risk factors for PND is key to early detect women at increased risk of developing this condition. We applied a machine learning (ML) approach to data from a multicenter cohort study on sleep and mood changes during the perinatal period ("Life-ON") to derive models for PND risk prediction in a cross-validation setting. A wide range of sociodemographic variables, blood-based biomarkers, sleep, medical, and psychological data collected from 439 pregnant women, as well as polysomnographic parameters recorded from 353 women, were considered for model building. These covariates were correlated with the risk of future depression, as assessed by regularly administering the Edinburgh Postnatal Depression Scale across the perinatal period. The ML model indicated the mood status of pregnant women in the first trimester, previous depressive episodes and marital status, as the most important predictors of PND. Sleep quality, insomnia symptoms, age, previous miscarriages, and stressful life events also added to the model performance. Besides other predictors, sleep changes during early pregnancy should therefore assessed to identify women at higher risk of PND and support them with appropriate therapeutic strategies.

Sleep and sleep disorders during pregnancy and postpartum: The Life-ON study.

OBJECTIVE: to prospectively assess sleep and sleep disorders during pregnancy and postpartum in a large cohort of women. METHODS: multicenter prospective Life-ON study, recruiting consecutive pregnant women at a gestational age between 10 and 15 weeks, from the local gynecological departments. The study included home polysomnography performed between the 23rd and 25th week of pregnancy and sleep-related questionnaires at 9 points in time during pregnancy and 6 months postpartum. RESULTS: 439 pregnant women (mean age 33.7 ± 4.2 yrs) were enrolled. Poor quality of sleep was reported by 34% of women in the first trimester of pregnancy, by 46% of women in the third trimester, and by as many as 71% of women in the first month after delivery. A similar trend was seen for insomnia. Excessive daytime sleepiness peaked in the first trimester (30% of women), and decreased in the third trimester, to 22% of women. Prevalence of restless legs syndrome was 25%, with a peak in the third trimester of pregnancy. Polysomnographic data, available for 353 women, revealed that 24% of women slept less than 6 h, and 30.6% of women had a sleep efficiency below 80%. Sleep-disordered breathing (RDI≥5) had a prevalence of 4.2% and correlated positively with BMI. CONCLUSIONS: The Life-ON study provides the largest polysomnographic dataset coupled with longitudinal subjective assessments of sleep quality in pregnant women to date. Sleep disorders are highly frequent and distributed differently during pregnancy and postpartum. Routine assessment of sleep disturbances in the perinatal period is necessary to improve early detection and clinical management.

Clinical and instrumental features in 82 patients with insufficient sleep syndrome.

Insufficient sleep syndrome possibly represents the worldwide leading cause of daytime sleepiness, but remains poorly recognised and studied. The aim of this case series is to comprehensively describe a cohort of patients with insufficient sleep syndrome. Eighty-two patients were studied concerning demographic and socio-economic features, medical, psychiatric and sleep comorbidities, substance use, sleep symptoms, actigraphy, video-polysomnography, multiple sleep latency tests and treatment. The typical patient with insufficient sleep syndrome is a middle-aged adult (with no difference of gender), employed, who has a family, often carrying psychiatric and neurological comorbidities, in particular headache, anxiety and depression. Other sleep disorders, especially mild sleep apnea and bruxism, were common as well. Actigraphy was a valuable tool in the characterisation of insufficient sleep syndrome, showing a sleep restriction during weekdays, associated with a recovery rebound of night sleep during weekends and a high amount of daytime sleep. An over- or underestimation of sleeping was common, concerning both the duration of night sleep and daytime napping. The average daily sleep considering both daytime and night-time, weekdays and weekends corresponds to the recommended minimal normal duration, meaning that the burden of insufficient sleep syndrome could mainly depend on sleep fragmentation and low quality. Sleep efficiency was elevated both in actigraphy and video-polysomnography. Multiple sleep latency tests evidenced a tendency toward sleep-onset rapid eye movement periods. Our study offers a comprehensive characterisation of patients with insufficient sleep syndrome, and clarifies their sleeping pattern, opening avenues for management and treatment of the disorder. Current options seem not adapted, and in our opinion a cognitive-behavioural psychotherapy protocol should be developed.

A series of 7 cases of patients with narcolepsy with hypocretin deficiency without the HLA DQB1*06:02 allele.

STUDY OBJECTIVES: We report data collected from 2 reference European sleep centers on a series of patients with narcolepsy with hypocretin-1 deficiency and absence of the human leukocyte antigens (HLA) DQB1*06:02 allele. METHODS: Clinical data, HLA DQ markers, and cerebrospinal fluid assessments were collected retrospectively from Caucasian patients with a diagnosis of narcolepsy type 1 with cerebrospinal fluid hypocretin-1 deficiency (< 110 pg/ml) and absence of the HLA DQB1*06:02 allele, with follow-up with at least 1 visit within the last 4 years, consecutively admitted to 2 European sleep centers (Lugano, Switzerland and Montpellier, France). RESULTS: Seven patients (3 of 29 patients in Lugano and 4 of 328 in Montpellier) were diagnosed with narcolepsy with hypocretin-1 deficiency and absence of HLA DQB1*06:02 (ie, 2% of patients with narcolepsy type 1). Regarding the HLA-DQB1 genotyping, 4 cases were positive for HLA DQB1*03:01, 1 for DQB1*03:02, and 3 for DQB1*02:01. Three patients had atypical cataplexy and 1 had no cataplexy. Only 2 patients had both a mean sleep latency of less than 8 minutes and more than 2 sleep onset rapid eye movement periods on the Multiple Sleep Latency Test, indicative of a less severe condition. CONCLUSIONS: Although rare, this series of 7 cases confirms that hypocretin-deficient narcolepsy should not be excluded in the absence of HLA DQB1*06:02, especially if patients are carriers of other high-risk HLA-DQB1 alleles (DQB1*03:01, *03:02, *02:01). These data support the hypothesis that narcolepsy type 1 is a wider disease spectrum linked to the loss of hypocretin peptide. CITATION: Miano S, Barateau L, De Pieri M, et al. A series of 7 cases of patients with narcolepsy with hypocretin deficiency without the HLA DQB1*06:02 allele. J Clin Sleep Med. 2023;19(12):2053-2057.

Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis.

STUDY OBJECTIVES: Periodic limb movements during sleep (PLMS) are a frequent finding in restless legs syndrome, but their impact on sleep is still debated, as well the indication for treatment. We systematically reviewed the available literature to describe which drug categories are effective in suppressing PLMS, assessing their efficacy through a meta-analysis, when this was possible. METHODS: The review protocol was preregistered on PROSPERO (CRD42021175848), and the systematic search was conducted on and EMBASE (last searched on March 2020). We included original human studies, which assessed PLMS modification on drug treatment with a full-night polysomnography, through surface electrodes on each tibialis anterior muscle. When at least 4 studies were available on the same drug or drug category, we performed a random-effect model meta-analysis. RESULTS: Dopamine agonists like pramipexole and ropinirole resulted the most effective, followed by l-dopa and other dopamine agonists. Alpha2delta ligands are moderately effective as well opioids, despite available data on these drugs are much more limited than those on dopaminergic agents. Valproate and carbamazepine did not show a significant effect on PLMS. Clonazepam showed contradictory results. Perampanel and dypiridamole showed promising but still insufficient data. The same applies to iron supplementation. CONCLUSIONS: Dopaminergic agents are the most powerful suppressors of PLMS. However, most therapeutic trials in restless legs syndrome do not report objective polysomnographic findings, there is a lack of uniformity in presenting results on PLMS. Longitudinal polysomnographic interventional studies, using well-defined and unanimous scoring criteria and endpoints on PLMS are needed. CITATION: Riccardi S, Ferri R, Garbazza C, Miano S, Manconi M. Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis. J Clin Sleep Med. 2023;19(4):811-822.

Influence of chronotype on the incidence and severity of perinatal depression in the "Life-ON" study.

BACKGROUND: Perinatal depression (PND) is a severe complication of pregnancy, but there are no established risk factors predicting the disease. Evening chronotype has been associated with unhealthy lifestyle habits and adverse outcomes during pregnancy. In this study, we aimed to clarify whether chronotype can predict symptoms and/or occurrence of PND. METHODS: Two hundred ninety-nine women were followed-up from the first trimester of pregnancy until 6 months postpartum. Chronotype was assessed at baseline using the MEQ, while mood was repeatedly assessed by depression rating scales (EPDS, HDRS, MADRS). The influence of time and chronotype on EPDS, HDRS and MADRS, was estimated by constructing multilevel linear mixed regression models. A Cox proportional-hazard regression model was built to evaluate the association between chronotype and incidence of depression. RESULTS: Chronotype modulated PND symptom severity depending on time of assessment, with evening chronotypes having a higher risk for developing PND symptoms, as assessed by EPDS, at postpartum visits V4 (5-12 days) and V5 (19-26 days). These also had less healthy lifestyle habits and were more likely to suffer from gestational diabetes mellitus and undergo cesarean delivery as compared to other chronotypes. LIMITATIONS: Only a minority of women were classified as evening chronotypes. The long follow-up phase of the study led to missing data. CONCLUSIONS: Pregnant evening chronotypes show unhealthy lifestyle habits and sociodemographic characteristics commonly associated with a higher risk for PND. They also have a higher risk of developing PND symptoms in the first month after delivery. Chronotype should therefore be routinely assessed during pregnancy to identify women potentially at risk for developing PND.

High-density EEG power topography and connectivity during confusional arousal.

Confusional arousal is the milder expression of a family of disorders known as Disorders of Arousal (DOA) from non-REM sleep. These disorders are characterized by recurrent abnormal behaviors that occur in a state of reduced awareness for the external environment. Despite frequent amnesia for the nocturnal events, when actively probed, patients are able to report vivid hallucinatory/dream-like mental imagery. Traditional (low-density) scalp and stereo-electroencephalographic (EEG) recordings previously showed a pathological admixture of slow oscillations typical of NREM sleep and wake-like fast-mixed frequencies during these phenomena. However, our knowledge about the specific neural EEG dynamics over the entire brain is limited. We collected 2 consecutive in-laboratory sleep recordings using high-density (hd)-EEG (256 vertex-referenced geodesic system) coupled with standard video-polysomnography (v-PSG) from a 12-year-old drug-naïve and otherwise healthy child with a long-lasting history of sleepwalking. Source power topography and functional connectivity were computed during 20 selected confusional arousal episodes (from -6 to +18 sec after motor onset), and during baseline slow wave sleep preceding each episode (from - 3 to -2 min before onset). We found a widespread increase in slow wave activity (SWA) theta, alpha, beta, gamma power, associated with a parallel decrease in the sigma range during behavioral episodes compared to baseline sleep. Bilateral Broadman area 7 and right Broadman areas 39 and 40 were relatively spared by the massive increase in SWA power. Functional SWA connectivity analysis revealed a drastic increase in the number and complexity of connections from baseline sleep to full-blown episodes, that mainly involved an increased out-flow from bilateral fronto-medial prefrontal cortex and left temporal lobe to other cortical regions. These effects could be appreciated in the 6 sec window preceding behavioral onset. Overall, our results support the idea that DOA are the expression of peculiar brain states, compatible with a partial re-emergence of consciousness.

Polysomnographic features of pregnancy: A systematic review.

Symptoms of sleep disturbances are common among pregnant women and generally worsen across gestation. Pregnancy-related sleep disorders are not only associated with a poor quality of life of the affected mothers, but also with adverse perinatal outcomes, including perinatal depression, gestational diabetes, preeclampsia, and preterm birth. The current knowledge about the impact of sleep disorders during pregnancy largely derives from the results of sleep surveys conducted in various populations. However, the number of studies examining changes in objective sleep variables during pregnancy via polysomnography has progressively increased in recent years. Here we systematically reviewed the polysomnographic studies available in the literature with the aim to describe the sleep pattern and to identify possible markers of sleep disruption in pregnant women. Based on our analysis, subjective worsening of sleep quality across gestation is related to objective changes in sleep macrostructure, which become particularly evident in the third trimester. Pregnancy per se does not represent an independent risk factor for developing major polysomnography-assessed sleep disorders in otherwise healthy women. However, in women presenting predisposing factors, such as obesity or hypertension, physiological changes occurring during pregnancy may contribute to the onset of pathological conditions, especially sleep-disordered breathing, which must be carefully considered.

Arousal responses to respiratory events during sleep: the role of pulse wave amplitude.

The study aims at assessing the changes in electroencephalography (as measured by the A-phases of cyclic alternating pattern) and autonomic activity (based on pulse wave amplitude) at the recovery of airway patency in patients with obstructive sleep apnea syndrome. Analysis of polysomnographic recordings from 20 male individuals with obstructive sleep apnea syndrome was carried out in total sleep time, non-rapid eye movement and rapid eye movement sleep. Scoring quantified the combined occurrence (time range of 4 s before and 4 s after respiratory recovery) or separate occurrence of A-phases (cortical activation), and pulse wave amplitude drops (below 30%) to apneas, hypopneas or flow limitation events. A dual response (A-phase associated with a pulse wave amplitude drop) was the most frequent response (71.8% in total sleep time) for all types of respiratory events, with a progressive reduction from apneas to hypopneas and flow limitation events. The highly significant correlation in total sleep time (r = 0.9351; P < 0.0001) between respiratory events combined with A-phases and respiratory events combined with pulse wave amplitude drops was confirmed both in non-rapid eye movement (r = 0.9622; P < 0.0001) and rapid eye movement sleep (r = 0.7162; P < 0.0006). In conclusion, a dual cortical and autonomic activation is the most common manifestation at the recovery of airway patency. The significant correlation between A-phases and relevant pulse wave amplitude drops suggests a possible role of pulse wave amplitude as a marker of cerebral response to respiratory events.

Sleep-Related Rhythmic Movement Disorder and Obstructive Sleep Apnea in Five Adult Patients.

ABSTRACT: Sleep-related rhythmic movements (SRRMs) are typical in infancy and childhood, where they usually occur at the wake-to-sleep transition. However, they have rarely been observed in adults, where they can be idiopathic or associated with other sleep disorders including sleep apnea. We report a case series of 5 adults with sleep-related rhythmic movement disorder, 4 of whom had a previous history of SRRMs in childhood. SRRMs mostly occurred in consolidated sleep, in association with pathological respiratory events, predominantly longer ones, especially during stage R sleep, and recovered in 1 patient with continuous positive airway pressure therapy. We hypothesize that sleep apneas may act as a trigger of rhythmic motor events through a respiratory-related arousal mechanism in genetically predisposed subjects.

OSA and Prolonged Oxygen Desaturation During Sleep are Strong Predictors of Poor Outcome in IPF.

PURPOSE: Sleep Breathing Disorders (SBD) are frequently found in idiopathic pulmonary fibrosis (IPF) and they are associated with worse quality of sleep and life and with higher mortality. The study aimed at evaluating the impact of SBD on prognosis (mortality or disease progression) in 35 patients with mild to moderate IPF. METHODS AND RESULTS: Obstructive sleep apnea (OSA) was diagnosed in 25/35 patients with IPF: 14/35 mild, 7/35 moderate, and 4/35 severe. According to the American Academy of Sleep Medicine (AASM) definition, sleep-related hypoxemia was found in 9/35 patients with IPF. According to the presence/absence of SBD, IPF patients were divided into 4 groups: NO-SBD group (Group A, 25.7%), OSA without sleep-related hypoxemia (Group B, 48.5%), OSA with sleep-related hypoxemia group (Group C, 22.8%), and only 1/35 had sleep-related hypoxemia without OSA(Group D, 2.8%). Statistical analysis was focused only on group A, B, and C. Patients with OSAS and sleep-related hypoxemia (Group C) had the worse prognosis, both in terms of mortality or clinical deterioration. SBD were the only independent risk factor (Cox Proportional Hazards Multiple Regression Analysis) for mortality (HR 7.6% IC 1.2-36.3; p = 0.029) and disease progression (HR 9.95% IC 1.8-644.9; p = 0.007). CONCLUSIONS: SBD are associated with a worse prognosis, both in terms of mortality or clinical progression. The presence of SBD should be explored in all IPF patients.

Sleep and respiratory sleep disorders in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) characterized by inflammation and progressive scarring of the lung parenchyma. IPF profoundly affects the quality of life (QoL) and fatigue is a frequently disabling symptom. The cause of fatigue is not well understood but patients with IPF often report extremely poor sleep quality and sleep-related breathing disorders (SRBD) that correlate with QoL. IPF patients present alterations in sleep architecture, including decreased sleep efficiency, slow wave sleep and rapid eye movement (REM) sleep, and increased sleep fragmentation. Moreover, sleep related hypoventilation during the vulnerable REM sleep period and obstructive sleep apnea-hypopnea syndrome (OSAHS) are frequent, but remain usually underdiagnosed. These SRBD in IPF are associated with alterations of the sleep structure, reduction of QoL and increased risk of mortality. In the absence of an effective therapy for IPF, optimizing the QoL could become the primary therapeutic goal. In this perspective the diagnosis and treatment of SRBD could significantly improve the QoL of IPF patients.

Can sleep microstructure improve diagnosis of OSAS? Integrative information from CAP parameters.

PURPOSE: The scoring of American Academy of Sleep Medicine (AASM) arousal is mandatory for the definition of respiratory event-related arousal (RERA). However there are other EEG activation phenomena, such as A phases of cyclic alternating pattern (CAP) which are associated with respiratory events in non rapid eye movements (NREM) sleep. This study aims at quantifying the additional value of CAP for the definition of respiratory events and sleep alterations in OSAS. METHODS: Analysis of polysomnographic recordings from nineteen OSAS patients was carried out. Scoring was focused on investigation of the cerebral response to flow limitation (FL) events. For this purpose we used both CAP rules and AASM arousal criteria. MAIN RESULTS: While no difference was demonstrated in the arousal index between mild and moderate-severe OSAS patients, CAP time showed a progressive enhancement from normal subjects (152.5±20.76) to mild (180.64±34.76) and moderate-severe (282.27±58.02) OSAS patients. In NREM sleep, only 41.1% of FL events met the criteria for the definition of RERA, while, 75.5% of FL events ended with a CAP A phase and most FL CAP (69.1%) terminated with a CAP phase A3 subtype. CONCLUSIONS: Our data indicate that the RERA scoring has a limited accuracy in the detection of FL events. In NREM sleep, CAP rules provided more information than AASM arousal for the definition of respiratory events and sleep alterations in OSAS.

Effects of antiepileptic treatment on sleep and seizures in nocturnal frontal lobe epilepsy.

OBJECTIVE: To study the effects of antiepileptic treatment on sleep parameters and video-polysomnography (VPSG) seizures in nocturnal frontal lobe epilepsy (NFLE). METHODS: Twenty patients with a clinical and VPSG diagnosis of NFLE (baseline polysomnography [PSG]) underwent a clinical follow-up and performed a second VPSG after effective antiepileptic treatment lasting for at least 6 months. Conventional sleep measures, cyclic alternating pattern (CAP) parameters, and objective VPSG seizures were assessed in NFLE patients before and after treatment and were compared with the results of 20 age- and gender-matched control subjects. RESULTS: Antiepileptic treatment determined a partial reduction of objective VPSG seizures of approximately 25% compared to baseline condition. Alterations of most conventional sleep measures recovered normal values, but nonrapid eye movement (NREM) sleep instability remained pathologically enhanced (CAP rate, +26% compared to controls) and was associated with persistence of daytime sleepiness. CONCLUSIONS: Residual epileptic events and high levels of unstable NREM sleep can define a sort of objective resistance of both seizures and disturbed arousal system to the therapeutic purpose of the antiepileptic drugs in NFLE. This finding could determine the need for new therapeutic options in this particular form of epilepsy.

Atypical patterns in portable monitoring for sleep apnoea: features of nocturnal epilepsy?

Atypical cardiorespiratory patterns can be found during routine clinical use of portable monitoring for diagnosis of sleep-disordered breathing (SDB). Over 1,000 consecutive portable recordings were analysed to study the potential ictal nature of stereotyped cardiorespiratory and motor patterns. Snoring, airflow, thoracic effort, pulse rate, body position, oxygen saturation and activity of the anterior tibialis muscles were quantified. Recordings showing stereotyped polygraphic patterns recurring throughout the night, but without the features of sleep apnoea (apnoea/hypopnoea index <5 events·h(-1)), were selected for investigation. Once included in the study, patients underwent attended nocturnal video polysomnography. A total of 15 recordings showing repeated polygraphic patterns characterised by a sequence of microphone activation, respiratory activity atypical for sleep and wakefulness, heart rate acceleration and limb movements, followed by body position change, were selected for investigation. Once included in the study, patients underwent attended nocturnal video polysomnography that showed frontal epileptic discharges triggering periodic electroencephalographic arousals, autonomic activation and stereotyped motor patterns. A diagnosis of nocturnal frontal lobe epilepsy (NFLE) was established for all patients. NFLE should be taken into consideration in patients with stereotyped and recurrent behavioural features during portable monitoring carried out for diagnosis of SDB.

Distinctive polysomnographic traits in nocturnal frontal lobe epilepsy.

PURPOSE: To describe the polysomnographic features and distribution of epileptic motor events, in relation to conventional sleep measures and cyclic alternating pattern (CAP) parameters, in 40 untreated patients with nocturnal frontal lobe epilepsy (NFLE). METHODS: We analyzed the basal polysomnographic recordings of 40 patients (20 male and 20 female; mean age: 31 ± 10 years) with a diagnosis of nocturnal frontal lobe epilepsy. Conventional sleep measures and CAP parameters were assessed. Polysomnographic recordings were subdivided in sleep cycles. The distribution of the epileptic motor events (including minor motor events, paroxysmal arousals, tonic-dystonic, or hyperkinetic seizures and epileptic nocturnal wandering) was analyzed throughout: total sleep time, non-rapid eye movement (NREM) and REM sleep, light sleep (S1 + S2), slow wave sleep (SWS), each sleep cycle, CAP or non-CAP sleep, phase A and phase B of CAP. Only clear epileptic motor events supported by video-polysomnographic evidence were taken into consideration. Polysomnographic findings of patients with NFLE were compared with those of 24 age- and gender-balanced healthy subjects without sleep complaints. KEY FINDINGS: Compared to controls, patients with NFLE showed a significant increase in wake after sleep onset, SWS duration, and REM latency, whereas REM sleep duration was significantly lower in NFLE patients. The patients with NFLE showed a significant increase of CAP time, CAP rate (72% vs. 32% in control group), CAP cycles, and mean duration of a CAP sequence. These findings were associated with a significant enhancement of all subtypes of the A phases of CAP (mainly subtype A1). A total of 139 epileptic motor events supported by video-polysomnographic evidence were counted: 98% of all seizures occurred in NREM sleep and 72% of NREM seizures emerged from SWS, the latter being particularly collected in the first sleep cycles and decreasing in frequency together with the progressive decline of deep sleep. Ninety percent of total NREM seizures occurred during a CAP sequence, and CAP-related seizures occurred in association with a phase A. SIGNIFICANCE: Significant polysomnographic alterations seem to emerge in patients with NFLE (increased REM latency, epileptic fragmentation of SWS, and increase of CAP rate). The analysis of seizure distribution showed that most epileptic events occurred in SWS, with predominance in the first sleep cycle and decreasing in frequency together with the homeostatic decline of SWS across the night. Within the NREM sleep, CAP is a manifestation of unstable sleep and represents a powerful predisposing condition for the occurrence of nocturnal motor seizures, which arise in concomitance with a phase A.

Giant nodular pseudoangiomatous stromal hyperplasia (PASH) of the breast presenting as a rapidly growing tumour.

Pseudoangiomatous stromal hyperplasia (PASH) is often a microscopic incidental finding in breast biopsies performed for benign or malignant diseases. In rare cases, it presents as a localised breast mass. Since Vuitch et al first described this condition in 1986, only 109 cases of PASH presenting as a palpable or mammographically detectable mass have been documented. PASH is characterised by a dense, collagenous proliferation of mammary stroma, forming inter-anastomosing capillary-like spaces. It is important to distinguish this benign lesion from a low-grade angiosarcoma. Here we describe the clinical, radiological and histological features of a very unusual case of PASH that presented as a rapidly growing breast lesion in a 37-year old woman.

Quality of life and psychological distress in locally advanced cervical cancer patients administered pre-operative chemoradiotherapy.

OBJECTIVE: The aim of the study was to analyze the Quality of life (QoL) scores in a single institution series of locally advanced cervical cancer patients (LACC) administered preoperative chemoradiation, compared to early stage disease (ECC) patients undergoing radical surgery. METHODS: The following criteria were required in order to enroll patients: age between 18 and 65years at initial diagnosis, at least 12 months from the end of treatment, no evidence of recurrence/second malignancy. The SF-36 questionnaire on general health, and the HADS questionnaire on mental distress were utilized. RESULTS: 93 subjects were available for the analysis. At time of analysis, median follow-up was 30 months (range 12-120). LACC patients showed QoL scores comparable to ECC patients with the exception of physical functioning (mean+/-SD=69.0+/-13.1 versus mean+/- SD=85.4+/-16.2, p value=0.0007). In the group of LACC patients, the presence of co-morbidities was significantly associated with the impairment of almost all subscales of QoL. A low education level and the status of unemployment were documented to negatively impact on the vast majority of SF-36 subscale scores. In the multivariate analysis, the presence of co-morbidities, low educational level, age> 50 years, and unemployment maintained their independent negative association with poor QoL scores. The percentage of cases with high levels HADS-anxiety was higher in LACC than ECC patients (27.6% versus 8.6%, p value=0.034). CONCLUSIONS: LACC patients administered preoperative chemoradiation showed QoL scores comparable to EEC patients, and a higher proportion of anxiety disorders; low educational level and unemployment status were mainly associated with poor QoL scores.