Risk factors for metastatic cutaneous squamous cell carcinoma: Refinement and replication based on 2 nationwide nested case-control studies.

BACKGROUND: Risk factors for cutaneous squamous cell carcinoma (cSCC) metastasis have been investigated only in relatively small data sets. OBJECTIVE: To analyze and replicate risk factors for metastatic cSCC. METHODS: From English and Dutch nationwide cancer registry cohorts, metastatic cases were selected and 1:1 matched to controls. The variables were extracted from pathology reports from the National Disease Registration Service in England. In the Netherlands, histopathologic slides from the Dutch Pathology Registry were revised by a dermatopathologist. Model building was performed in the English data set using backward conditional logistic regression, whereas replication was performed using the Dutch data set. RESULTS: In addition to diameter and thickness, the following variables were significant risk factors for metastatic cSCC in the English data set (n = 1774): poor differentiation (odds ratio [OR], 4.56; 95% CI, 2.99-6.94), invasion in (OR, 1.69; 95% CI, 1.05-2.71)/beyond (OR, 4.43; 95% CI, 1.98-9.90) subcutaneous fat, male sex (OR, 2.59; 95% CI, 1.70-3.96), perineural/lymphovascular invasion (OR, 2.12; 95% CI, 1.21-3.71), and facial localization (OR, 1.57; 95% CI, 1.02-2.41). Diameter and thickness showed significant nonlinear relationships with metastasis. Similar ORs were observed in the Dutch data set (n = 434 cSCCs). LIMITATIONS: Retrospective use of pathology reports in the English data set. CONCLUSION: cSCC staging systems can be improved by including differentiation, clinical characteristics such as sex and tumor location, and nonlinear relationships for diameter and thickness.

Progression of Large Vessel Disease in Patients With Giant Cell Arteritis-Associated Ischemic Stroke: The Role of Vascular Imaging: A Case Series.

OBJECTIVE: Giant cell arteritis (GCA) can cause ischemic stroke (IS) due to the involvement of the internal carotid and vertebral arteries. The aim of our study is to describe the pattern of stroke recurrence in patients with GCA-related IS and the role of vascular imaging in the follow-up of these patients. METHODS: We conducted an observational study of 2417 consecutive patients diagnosed with IS and admitted to our hospital from January 2012 to December 2018. We reviewed patients with GCA-related IS and the relationship of erythrocyte sedimentation rate, C-reactive protein, vascular status, and clinical course. RESULTS: We found 4 patients with GCA-related IS among 2417 IS patients: 1 woman (25%); median age, 77.3 years (67-85 years). Mean follow-up was 3.6 years. Initial vascular workup showed vertebral artery stenosis in all of them and internal carotid artery stenosis in 2 patients. All patients were started on treatment with full-dose prednisone, associated with methotrexate in 2 cases. Follow-up color-coded duplex sonography disclosed progression of arterial stenoses in 3 patients who suffered a recurrent IS (days after index stroke; mean, 27.67 [SD, 10.97]) despite normal C-reactive protein and erythrocyte sedimentation rate values. CONCLUSIONS: Vascular imaging, especially with color-coded duplex sonography, could play a role in the follow-up of patients with GCA-related IS and identify those patients with higher risk of recurrent stroke.

Primary molar infraocclusion: frequency, magnitude, root resorption and premolar agenesis in a Spanish sample.

AIM: This study was conducted to determine frequency, distribution and magnitude of infraocclusion in primary mandibular molars; to evaluate root resorption, the frequency of premolars agenesis and the association between primary molar infraocclusion and premolar agenesis. MATERIALS AND METHODS: The sample consisted of 472 children who were subdivided in 3 age groups. The magnitude of infraocclusion was determined following the Bjerklin and Bennett method modified by the authors. Radicular resorption was determined using the rating scale proposed by Bjerklin and Bennett evaluating mesial and distal roots separately. The development degree of corresponding premolars was determined using the Demirjian method. RESULTS: One hundred and three (21.8%) children presented infraocclusion. The first primary molar presented infraocclusion in a significantly higher frequency. Considering the 3 scores of infraocclusion, 61.1% of the affected molars were classified as mild infraocclusion. No differences were found considering the root resorption pattern for primary molars, infraoccluded or not. Significant differences were found in the presence of agenesis in the group of infraoccluded molars. CONCLUSION: The present study identified a high percentage of infraocclusion, demonstrating that the type of molar is an influent variable, that the first primary molar is the most affected one, especially mandibular molars, and that the majority was mainly of a mild degree. There were no significant differences between the exfoliation of infraoccluded and non infraoccluded primary molars. However, radicular resorption of infraoccluded molars presented a clear delay or was totally absent in infraoccluded molars associated with premolar agenesis. Significant differences in the presence of agenesis beneath infraoccluded molars were observed.

[Selective embolization to treat obstetric hemorrhage]. / Embolización selectiva como tratamiento de la hemorragia obstétrica.

OBJECTIVE: To describe cases of obstetric hemorrhage that have called for selective intra-arterial embolization and the different embolization techniques used. To assess the clinical outcomes and postprocedural fertility. MATERIAL AND METHODS: We studied 27 women with obstetric hemorrhage. In 24 patients, embolization was performed by catheterizing both uterine arteries and in 2 patients only one uterine artery was catheterized (pseudoaneurysm). The materials used for embolization consisted of Spongostan in 17/27, particles in 9/27, and coils in 1/27. Clinical follow-up included an analysis of early and late complications and of postprocedural fertility. RESULTS: Hemorrhage was classified as primary (25/27) or secondary (2/27). The cause of bleeding was vaginal delivery (20), cesarean sections (5), abortion (1), and cervical ectopic pregnancy (1). The initial technical success rate was 100% and the clinical success rate was 92.6% (25 of the 27 patients). Bleeding ceased and the outcome was satisfactory in 25 patients. During clinical follow-up ranging from one to seven years, 23 patients had normal menstruation and 6 patients completed 7 full-term pregnancies. CONCLUSION: Intra-arterial embolization for obstetric hemorrhage leads to good outcomes and few complications and it preserves fertility.

[Cognitive impairment? Don't forget neurolues]. / Geheugenklachten? Vergeet neurolues niet.

BACKGROUND: Cognitive disorders usually develop slowly over years and are mainly caused by untreatable neurodegenerative disorders. Rapidly progressive cognitive disorders should raise suspicion of an underlying and treatable psychiatric, internal or neurological condition. Timely recognition of these conditions is important. CASE: We present the case of a 68-year old man, presenting on the emergency department with a history of progressive cognitive impairment since several weeks. Cerebral MRI showed T2-hyperintensities in the left hippocampal, mesotemporal and insular regions; lesser so in the right mesotemporal region. After initial treatment for herpesencephalitis and autoimmune encephalitis, we diagnosed neurolues and started treatment with benzylpenicillin. CONCLUSION: It may be difficult to diagnose neurolues because the vast variety of clinical symptoms and radiological signs. This case shows that neurolues should be considered in a patient with rapidly progressive cognitive disorders and that neurolues can mimic a herpesencephalitis or an autoimmune encephalitis. Timely recognition is important to prevent irreversible damage.

Eating through time: Understanding dietary practices across late prehistory in the northeastern Iberian Peninsula.

OBJECTIVE: This study seeks to contribute to the current understanding of dietary variation in the late Prehistory of the northeastern Iberian Peninsula by examining buccal dental microwear patterns alongside archeological data from the same populations. MATERIALS AND METHODS: Teeth from 84 adult individuals from eight distinct samples spanning the Middle-Late Neolithic to the Middle Bronze Age (Cova de l'Avi, Cova de Can Sadurní, Cova de la Guineu, Cova Foradada, Cova del Trader, Roc de les Orenetes, Cova del Gegant, Cova dels Galls Carboners) were analyzed using optical microscopy to examine buccal dental microwear patterns. RESULTS: The analysis did not reveal clear chronological contrasts in the dietary habits of these samples. Nevertheless, significant differences emerged among the samples, leading to their classification into two distinct sets based on the abrasiveness of the diet informed by the microwear patterns. These findings offer similarities and differences among samples in the Iberian Peninsula, shedding light on the diverse lifestyles of these individuals. DISCUSSION: Integrating our new results with other available proxies points to a multifaceted specialization in dietary patterns among these samples, influenced by factors such as habitat, resource selection, and available technology. By contextualizing the results within the broader context of the Iberian Peninsula, this research discerns shared characteristics and distinctive adaptations in the dietary practices and subsistence strategies of these groups. Ultimately, this study contributes to a deeper understanding of the intricate interplay between culture and environment in shaping human diets throughout late Prehistory.

Transcriptome-wide mRNA condensation precedes stress granule formation and excludes stress-induced transcripts.

Stress-induced condensation of mRNA and proteins into stress granules is conserved across eukaryotes, yet the function, formation mechanisms, and relation to well-studied conserved transcriptional responses remain largely unresolved. Stress-induced exposure of ribosome-free mRNA following translational shutoff is thought to cause condensation by allowing new multivalent RNA-dependent interactions, with RNA length and associated interaction capacity driving increased condensation. Here we show that, in striking contrast, virtually all mRNA species condense in response to multiple unrelated stresses in budding yeast, length plays a minor role, and instead, stress-induced transcripts are preferentially excluded from condensates, enabling their selective translation. Using both endogenous genes and reporter constructs, we show that translation initiation blockade, rather than resulting ribosome-free RNA, causes condensation. These translation initiation-inhibited condensates (TIICs) are biochemically detectable even when stress granules, defined as microscopically visible foci, are absent or blocked. TIICs occur in unstressed yeast cells, and, during stress, grow before the appearance of visible stress granules. Stress-induced transcripts are excluded from TIICs primarily due to the timing of their expression, rather than their sequence features. Together, our results reveal a simple system by which cells redirect translational activity to newly synthesized transcripts during stress, with broad implications for cellular regulation in changing conditions.

Clinical impact of early brain atrophy in clinically isolated syndromes.

BACKGROUND: The impact of global and tissue-specific brain atrophy on conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS) is not fully gauged. OBJECTIVES: We aimed to determine the magnitude and clinical relevance of brain volume dynamics in the first year after a CIS. METHODS: We assessed 176 patients with CIS within 3 months of onset, clinically and by conventional magnetic resonance imaging (MRI) scans, at baseline and 1 year after clinical onset. We determined the percentage of brain volume change (PBVC) and the brain parenchymal (BPF), grey matter (GMF) and white matter (WMF) fractions. RESULTS: The mean follow-up time was 53 months (SD = 16.8): 76 patients (43%) experienced a second attack, 32 (18%) fulfilled MRI-only 2005 McDonald criteria and 68 (39%) remained as CIS. Statistically significant decreases in the volume measures tested were observed in patients with a second attack, for BPF and PBVC; in both MS groups for GMF; whereas in all groups, the WMF was unchanged. Patients with a second attack had larger PBVC decreases (- 0.65% versus + 0.059%; p < 0.001). PBVC decreases below - 0.817% independently predicted shorter times to a second attack. CONCLUSIONS: Global brain and grey matter volume loss occurred within the first year after a CIS; brain volume loss predicted conversion to MS.

Personalised decision making to predict absolute metastatic risk in cutaneous squamous cell carcinoma: development and validation of a clinico-pathological model.

Background: Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer, affecting more than 2 million people worldwide yearly and metastasising in 2-5% of patients. However, current clinical staging systems do not provide estimates of absolute metastatic risk, hence missing the opportunity for more personalised treatment advice. We aimed to develop a clinico-pathological model that predicts the probability of metastasis in patients with cSCC. Methods: Nationwide cohorts from (1) all patients with a first primary cSCC in The Netherlands in 2007-2008 and (2) all patients with a cSCC in 2013-2015 in England were used to derive nested case-control cohorts. Pathology records of primary cSCCs that originated a loco-regional or distant metastasis were identified, and these cSCCs were matched to primary cSCCs of controls without metastasis (1:1 ratio). The model was developed on the Dutch cohort (n = 390) using a weighted Cox regression model with backward selection and validated on the English cohort (n = 696). Model performance was assessed using weighted versions of the C-index, calibration metrics, and decision curve analysis; and compared to the Brigham and Women's Hospital (BWH) and the American Joint Committee on Cancer (AJCC) staging systems. Members of the multidisciplinary Skin Cancer Outcomes (SCOUT) consortium were surveyed to interpret metastatic risk cutoffs in a clinical context. Findings: Eight out of eleven clinico-pathological variables were selected. The model showed good discriminative ability, with an optimism-corrected C-index of 0.80 (95% Confidence interval (CI) 0.75-0.85) in the development cohort and a C-index of 0.84 (95% CI 0.81-0.87) in the validation cohort. Model predictions were well-calibrated: the calibration slope was 0.96 (95% CI 0.76-1.16) in the validation cohort. Decision curve analysis showed improved net benefit compared to current staging systems, particularly for thresholds relevant for decisions on follow-up and adjuvant treatment. The model is available as an online web-based calculator (https://emc-dermatology.shinyapps.io/cscc-abs-met-risk/). Interpretation: This validated model assigns personalised metastatic risk predictions to patients with cSCC, using routinely reported histological and patient-specific risk factors. The model can empower clinicians and healthcare systems in identifying patients with high-risk cSCC and offering personalised care/treatment and follow-up. Use of the model for clinical decision-making in different patient populations must be further investigated. Funding: PPP Allowance made available by Health-Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships.

Ancient DNA from an Early Neolithic Iberian population supports a pioneer colonization by first farmers.

The Neolithic transition has been widely debated particularly regarding the extent to which this revolution implied a demographic expansion from the Near East. We attempted to shed some light on this process in northeastern Iberia by combining ancient DNA (aDNA) data from Early Neolithic settlers and published DNA data from Middle Neolithic and modern samples from the same region. We successfully extracted and amplified mitochondrial DNA from 13 human specimens, found at three archaeological sites dated back to the Cardial culture in the Early Neolithic (Can Sadurní and Chaves) and to the Late Early Neolithic (Sant Pau del Camp). We found that haplogroups with a low frequency in modern populations-N* and X1-are found at higher frequencies in our Early Neolithic population (∼31%). Genetic differentiation between Early and Middle Neolithic populations was significant (F(ST) ∼0.13, P<10(-5)), suggesting that genetic drift played an important role at this time. To improve our understanding of the Neolithic demographic processes, we used a Bayesian coalescence-based simulation approach to identify the most likely of three demographic scenarios that might explain the genetic data. The three scenarios were chosen to reflect archaeological knowledge and previous genetic studies using similar inferential approaches. We found that models that ignore population structure, as previously used in aDNA studies, are unlikely to explain the data. Our results are compatible with a pioneer colonization of northeastern Iberia at the Early Neolithic characterized by the arrival of small genetically distinctive groups, showing cultural and genetic connections with the Near East.

The ParkinsonNet concept: development, implementation and initial experience.

The quality and efficiency of allied health care in Parkinson's disease (PD) must be improved. We have developed the ParkinsonNet concept: a professional regional network within the catchment area of hospitals. ParkinsonNet aims to: (1) improve PD-specific expertise among allied health personnel, by training a selected number of therapists according to evidence-based guidelines; (2) enhance the accuracy of referrals by neurologists; (3) boost patient volumes per therapist, by stimulating preferred referral to ParkinsonNet therapists; and (4) stimulate collaboration between therapists, neurologists, and patients. We describe the procedures for developing a ParkinsonNet network. Our initial experience with this new concept is promising, showing an increase in PD-specific and a steady rise in the patient volume of individual therapists.

Inhibiting cyclin-dependent kinase/cyclin activity for the treatment of cancer and cardiovascular disease.

Excessive cell proliferation contributes to the pathobiology of human diseases with a high health and socio-economic impact, including cancer and vascular occlusive diseases (e. g., atherosclerosis, in-stent restenosis, transplant vasculopathy, and vessel bypass graft failure). Recent advances in the understanding of the molecular networks governing the hyperplastic growth of tumors and vascular obstructive neointimal lesions have provided new perspectives for preventive and therapeutic strategies against these disorders. Mammalian cell proliferation requires the activation of several cyclin-dependent protein kinases (CDKs). Postranslational activation of CDKs is a complex process that involves their association with regulatory subunits called cyclins. The activity of CDK/cyclin holoenzymes is negatively regulated through their interaction with members of the CDK family of inhibitory proteins (CKIs). Moreover, over fifty low molecular weight pharmacological CDK inhibitors that target the ATP-binding pocket of the catalytic site of CDKs have been identified. In this review, we will discuss the use of pharmacological and gene therapy strategies against CDK/cyclins in animal models and clinical trials of cancer and cardiovascular disease.

Role of the growth suppressor p27Kip1 during vascular remodeling.

At homeostasis, vascular cells display a very low proliferative rate and a scant migratory activity. However, hyperplastic growth and locomotion of vascular cells are a hallmark of vascular remodeling during several pathophysiological conditions (e.g., neovascularization, arteriosclerosis and restenosis post-angioplasty). Thus, a better understanding of the molecular mechanisms that control vascular cell proliferation and migration should facilitate the development of novel therapies to treat cardiovascular disease. In this review, we will discuss recent studies implicating the cell cycle regulatory protein p27Kip1 as a key modulator of vascular cell growth and locomotion in vitro and during vascular remodeling in vivo.

Conductive deafness in aglossia.

Aglossia is a rare anomaly often accompanied with several congenital defects including varying degrees of limb deficiency, micrognathia and oral synechiae. We report on a girl with aglossia and persistent anterior buccopharyngeal membrane. Other anomalies observed on the patient were oesophageal atresia, hypoplastic epiglottis, ptosis of the left eyelid, and conductive deafness which is probably an additional symptom of this syndrome group.

Integrated multidisciplinary care in Parkinson's disease: a non-randomised, controlled trial (IMPACT).

BACKGROUND: A multidisciplinary approach is thought to be the best way to manage the motor and non-motor symptoms of Parkinson's disease, but how such care should be delivered is unknown. To address this gap in knowledge, we assessed the effectiveness of an integrated multidisciplinary approach compared with usual care. METHODS: We recruited patients for our non-randomised controlled trial from six community hospitals in the Netherlands (two in regions where the integrated care intervention was available and four in control regions that administered usual care). Eligible patients were those with Parkinson's disease, aged 20-80 years, and without severe cognitive impairment or comorbidity. Patients in the intervention group were offered an individually tailored comprehensive assessment in an expert tertiary referral centre and subsequent referrals to a regional network of allied health professionals specialised in Parkinson's disease. Primary outcomes were activities of daily living (Academic Medical Center linear disability score [ALDS]) and quality of life (Parkinson's disease quality of life questionnaire [PDQL]) measured at 4, 6, and 8 months. Secondary outcomes included motor functioning (unified Parkinson's disease rating scale, part III [UPDRS III], at 4 months), caregiver burden (belastungsfragebogen Parkinson angehörigen-kurzversion [BELA-A-k] at 4 and 8 months), and costs (during whole study period). Primary analysis was by intention to treat and included scores over 4, 6, and 8 months, with correction for baseline score. The trial is registered at Clinicaltrials.gov, number NCT00518791. FINDINGS: We recruited 301 patients (150 patients in the intervention group and 151 in the control group) between August, 2007, and December, 2009, of whom 285 completed follow-up (last follow-up was July, 2010). 101 (67%) patients in the intervention group visited the expert centre; 49 (33%) opted not to visit the expert centre. The average ALDS score from months 4, 6, and 8, with correction for baseline score, was greater in the intervention group than in the control group (difference 1·3 points, 95% CI -2·1 to 2·8; corresponding raw logit score difference 0·1, 95% CI 0·003 to 0·2) as was the average PDQL score (difference 3·0 points, 0·4 to 5·6). Secondary analysis with correction for baseline disease severity showed no differences between groups for ALDS (difference 0·9 points, 95% CI -0·6 to 2·4; corresponding raw logit score difference 0·1, -0·02 to 0·3) or PDQL (difference 1·7 points, -1·2 to 4·6). Secondary outcomes did not differ between groups (UPDRS III score difference 0·6 points, 95% CI -1·4 to 2·6; BELA-A-k score difference 0·8 points, -0·2 to 1·8; cost difference €742, -€489 to €1950). INTERPRETATION: This integrated care approach offered only small benefits to patients with Parkinson's disease, and these disappeared after correction for baseline disease severity. These results suggest that different approaches are needed to achieve more substantial health benefits. FUNDING: NutsOhra Foundation, Stichting Parkinson Nederland, National Parkinson Foundation.

Diagnosis of epileptic syndrome after a new onset seizure and its correlation at long-term follow-up: longitudinal study of 131 patients from the emergency room.

This study aims to demonstrate the reliability of the diagnosis of epilepsy after a new onset seizure, supported by a detailed anamnesis and the complementary tests accessible at the emergency room (ER), such as CT-scan and video-EEG. It was a prospective study including 131 adult patients (55% males, medium age 52.42 (±21.5)[16-98] years-old, follow-up 25.22 (±13.69)[12-31] months). In half of cases we could not identify any predisposing factor. Within the first 72 h, patients were included into an epileptic syndrome according to the ILAE 1989 classification, if possible. Thereafter, they were followed-up in the outpatient clinic of the Epilepsy Unit, where seizure recurrence was recorded and further diagnostic examinations were performed. 94.1% of patients initially diagnosed of epilepsy were confirmed as epileptics, and up to 57% of patients could be classified into a particular syndrome from the ER. Conversely, 44.6% of patients with the initial diagnosis of isolated seizure and one third of patients with non-epileptic seizures developed recurrence, switching their initial diagnosis to epilepsy. Both CT-scan and early EEG demonstrated its usefulness evaluating the risk of recurrence after a new onset seizure (Positive predictive value 78% and 88%, respectively). Epileptiform activity was a predictor of seizure recurrence (p<0.05), independently to the moment where the EEG was performed. According to our results, it is realistic to perform the diagnosis of epilepsy after a new onset seizure, although many patients still need further specific examinations, or seizure recurrence, to be diagnosed.

An observational study of the effectiveness and safety of natalizumab in the treatment of multiple sclerosis.

AIM: To analyse the safety and effectiveness of natalizumab in the treatment of multiple sclerosis in a real clinical practice setting and according to the approved indications. PATIENTS AND METHODS: All patients with multiple sclerosis treated with natalizumab in our centre were evaluated. The clinical and radiological disease activity during the first year of treatment was analyzed in patients who received at least 12 doses of the drug. The data regarding moderate and severe adverse events in the entire study sample was also evaluated. RESULTS: A total of 112 patients were included in the study, of which 110 had been previously treated with other drugs and 76 had received at least 12 doses of natalizumab. In this group, the annualized relapse rate was reduced by 89% compared to the preceding year and 80% of patients were free from relapses after one year of treatment. Nine percent of patients exhibited 3-month confirmed disability progression. At month 12, the mean number of gadolinium-enhancing lesions on brain MRI was decreased by 99% compared to the pre-treatment MRI. During the first year of treatment, 76% of patients remained free from clinical activity and 33% remained free from both clinical and radiological disease activity. Twenty-nine percent of patients had at least one moderate or severe adverse event, which led to treatment discontinuation in 6%. Four percent of patients experienced immediate hypersensitivity reactions. CONCLUSION: This study suggests that natalizumab is effective in reducing disease activity in patients with relapsing multiple sclerosis and inadequate response to other therapies, with a favorable risk-benefit ratio.

Genetic association of CASP8 polymorphisms with primary progressive multiple sclerosis.

We investigated caspase 8 (CASP8) as a candidate gene for multiple sclerosis (MS) susceptibility. Three SNPs (rs2037815, rs12990906 and rs1035140) were genotyped in 546 MS patients and 547 controls. For SNP rs2037815, GG homozygosity was associated with primary progressive multiple sclerosis (PPMS) when compared with relapse-onset MS and controls. We identified risk (GCA) and protective (ACT) haplotypes associated with PPMS when compared with relapse-onset MS and controls. GG homozygosity for SNP rs2037815 in PPMS patients was associated with a trend towards faster disease progression. These findings point to a role of CASP8 polymorphisms in the MS genetic risk in PPMS patients.

[A study of right-left shunt in transient global amnesia]. / Estudio de shunt derecha-izquierda en la amnesia global transitoria.

INTRODUCTION: Transient global amnesia (TGA) is a disorder of unknown aetiology. In recent studies, TGA was associated with a right to left shunt (RLS). We studied the presence of the RLS in patients with TGA and we compared this series with patients who had suffered a transient ischaemic attack (TIA). PATIENTS AND METHODS: We included 66 consecutive TGA patients. In these patients a transcranial Doppler was performed to determine the presence of a RLS. We collected data on the TGA episode, vascular risk factors, migraine history, recurrence of TGA and neuroimaging in patients with and without RLS. We compared the prevalence of the RLS in TGA series with 59 patients with TIA. RESULTS: The prevalence of RLS was 21.2% in patients with TGA. The RLS was associated with the migraine history (40% versus 13%; p = 0.014) and a Valsalva manoeuvre as a triggering factor (50% versus 14.5%; p = 0.022). A greater prevalence of RLS was detected in patients with TIA (55.9% versus 21.2%; p < 0.001). CONCLUSIONS: The RLS prevalence in TGA patients is similar to the general population but significantly lower than the prevalence in TIA patients. The association with a Valsalva manoeuvre as a precipitating factor in the TGA patients with RLS could play a role in the aetiopathogenesis of the TGA.