Restless legs syndrome in end-stage renal disease: Clinical characteristics and associated comorbidities

BackgroundDespite being frequently described in patients with end-stage renal disease (ESRD), clinical characteristics and comorbidities in association with restless legs syndrome (RLS) are still to be confirmed.ObjectivesThe aim of this study was to investigate clinical factors associated with RLS in ESRD patients in hemodialysis.MethodsThis is a cross-sectional study of 400 patients on hemodialysis, evaluating RLS, clinical features and other sleep abnormalities.ResultsOut of 400, 86 patients presented RLS (21.5%; mean age 48.8 ± 13.8 y), being more frequent in females (p < 0.005). Forty-eight individuals (12% mean age 50.7 ± 13.1 y) had moderate/severe RLS, 14 reported symptoms prior to hemodialysis, 13 described family history of RLS, and eight described symptoms as disturbing during dialysis. RLS cases showed lower hemoglobin (p < 0.005), poorer quality of sleep (Pittsburgh Sleep Quality Index >5, p = 0.002), higher scores on the Beck Depression Inventory Scale (p < 0.005), greater scores on the Charlson Comorbidity Index (p = 0.01) and the Epworth Sleepiness Scale (p = 0.001) and higher risk of obstructive sleep apnea (OSA; Berlin questionnaire, p = 0.01). Hypertension was more frequent in cases with moderate/severe RLS (p = 0.01) and remained after controlling for the risk of OSA (p = 0.02).ConclusionIn ESRD patients in hemodialysis, RLS is present in 21.5%; 16% report symptoms prior to hemodialysis and a family history of RLS. Symptoms are disturbing during hemodialysis in 9% of cases. RLS is associated with lower hemoglobin, worse sleep quality, excessive daytime sleepiness, depressive symptoms and higher risk of OSA. Hypertension is associated with moderate/severe RLS.     

Assessing health-related quality of life in patients with restless legs syndrome in Korea: Comparison with other chronic medical diseases

BackgroundThere have been few quality of life (QoL) studies of patients with restless legs syndrome (RLS) in Asian countries. We studied the QoL of patients with RLS and compared it to normal controls and patients with hypertension, type 2 diabetes, or osteoarthritis in Korea.MethodsA total of 215 RLS patients (141 female; mean age 51.7 ± 13.5) were enrolled. All patients completed the questionnaires, including all the Korean versions of SF-36, RLS QoL, the International RLS Severity scale (IRLS), the Pittsburgh Sleep Quality Index (PSQI), and the Beck Depression Inventory-2 (BDI-2). These results were compared with the scores from normal controls (N = 214) and from patients with hypertension (196), uncomplicated type 2 diabetes (185), or osteoarthritis of the knee (177).ResultsThe SF-36 QoL in patients with RLS was lower than that of the normal controls, and even lower than patients with hypertension or diabetes, but higher than those with osteoarthritis. The SF-36 Qol of RLS patients showed a significantly negative correlation with the severity of RLS symptoms (r = ?0.430, p < 0.001) and the severity of depression (r = ?0.565, p < 0.001), but was not significantly related to gender, age, or age-of-symptom onset (early or late-onset). Step-wise multiple regression identified three factors related to SF-36 QoL: depression (46.5% of RLS had responses on BDI-2 indicating depression) (β = ?.899, p < 0.001), RLS symptom severity (K-IRLS) (β = ?.718, p < 0.001), and gender (female) (β = ?6.128, p = 0.007).ConclusionsThese findings show that RLS has a considerable impact on the QoL of Koreans, which is comparable with studies of western countries. The QoL impairment relates to the degree of depression with RLS for Koreans.     

Voxel-based morphometry in unmedicated patients with restless legs syndrome

BackgroundThe pathophysiology of restless legs syndrome (RLS) is not yet understood. A prior voxel-based morphometry (VBM) study reported gray matter increase in the pulvinar of the thalamus in a group of patients, most of whom were on medical treatment. Since there is evidence that medication can change the volume of cerebral structures, the question arises as to whether the reported morphometric alterations are caused by the RLS itself or, alternatively, are a consequence of drug treatment. To address this issue, we performed VBM in unmedicated RLS patients.MethodsFourteen patients with idiopathic RLS with no (n = 11) or only minimal (n = 3) treatment exposure in the past and 14 age- and sex-matched healthy subjects were investigated. All subjects were free of psychotropic drugs for at least 4 months. Morphological data were analyzed by using optimized VBM.ResultsWe did not detect any structural changes except for slightly increased gray matter density in the ventral hippocampus (p = 0.046 on the left and p = 0.055 on the right side) and in the middle orbitofrontal gyrus (p = 0.046 on the right and p = 0.097 on the left side).ConclusionOur study could not confirm the findings of a prior study. A possible explanation for the divergent findings is the difference between the populations examined. Since, in our study, essentially treatment-naïve patients were investigated, it is possible that the prior findings reflect treatment-induced effects on cerebral morphology in RLS.     

Predictors of restless legs syndrome in pregnancy: A hospital based cross sectional survey from Pakistan

Restless legs syndrome (RLS) is more common in pregnant women. The objective of our study was to determine frequency of RLS in pregnant women and predictors of RLS in pregnancy in Pakistan. All pregnant women admitted at The Aga Khan University Hospital for delivery from June to July 2005 were enrolled. Eighty-one of 271 (30%) interviewed women fulfilled the diagnostic criteria of RLS. One hundred seventeen (43%) of the subjects dropped their haemoglobin during the pregnancy. No significant difference in haemoglobin drop was noted between the RLS group and healthy group. On multivariate analysis family history of RLS (OR: 8.43, CI: 2.32–30.57, p value < 0.001), history of RLS in prior pregnancy (OR: 53.74, CI: 6.72–429.8, p value < 0. 001), history of RLS in past even when non-pregnant (OR: 12.91, CI: 3.34–49.87, p value < 0.001) and haemoglobin of 11 g/dL or less (OR: 2.05, CI: 1.04–4.04, p value 0.036) were found to be independent predictors of RLS during pregnancy. Subgroup analysis revealed that family history of RLS (OR: 3.06, CI: 1.2–7.83, p value 0.019) and anemia (OR: 1.89, CI: 0.96–3.71, p value 0.06) were associated with de novo RLS, and family history of RLS (OR: 12.39, CI: 4.45–35.54, p value < 0.001) and multiparity (OR: 6.84, CI: 2.15–21.71, p value 0.001) were predictors of pre-existing RLS.     

The severity range of restless legs syndrome (RLS) and augmentation in a prospective patient cohort: Association with ferritin levels

ObjectivesThe aim of the study was to prospectively examine all patients with a diagnosis of RLS consulting a sleep disorders clinic and to assess RLS severity and augmentation and their associations, including ferritin levels.MethodsPatients were stratified into patients with RLS as ancillary diagnosis, RLS sufferers without current augmentation and RLS sufferers with current augmentation. Work-up included RLS severity scales and blood biochemical variables including indices of iron metabolism.ResultsIn an 18-month period, 302 patients with RLS (183 women, 119 men; mean age, 59.1 ± 13.7 years) were recruited. RLS was considered idiopathic in 291 patients (96.4%). Most patients (240, 79.5%) were RLS sufferers, whereas the remaining 62 (20.5%) had RLS as ancillary diagnosis. Nineteen out of 162 patients treated with dopaminergic agents (11.7%) had current augmentation. Almost one-third of all patients (31.1%) had ferritin levels <50 μg/l. Patients with an ancillary diagnosis of RLS had higher ferritin levels than RLS sufferers without current augmentation. The lowest ferritin levels were present in RLS sufferers with current augmentation 132.8 ± 98.0 μg/l vs. 100.6 ± 84.5 μg/l vs. 55.8 ± 43.6 μg/l; p = 0.002). Patients with augmentation did not differ from non-augmented patients regarding age, gender, RLS etiology, presence of previous augmentation, or any other documented comorbidity (p > 0.05).ConclusionThe severity spectrum of RLS in this clinical cohort ranged from the ancillary diagnosis of RLS to augmented RLS. There was an inverse correlation between RLS severity and ferritin levels. Patients with current augmentation had the lowest ferritin levels. Our data further strengthen a putative role of low iron stores as a potential aggravator of idiopathic RLS. Moreover, low ferritin might represent a potential biomarker of RLS augmentation under dopaminergic therapy.     

Medical comorbidity and distress in patients with irritable bowel syndrome: The moderating role of age

ObjectivesIrritable bowel syndrome (IBS) affects people across the age spectrum and is highly comorbid with other medical conditions. The aim of this study was to determine the moderating effect of age on the relationship between medical comorbidity and health outcomes in IBS patients.MethodsPatients (n = 384) across the age spectrum (18 to 70) completed questionnaires regarding medical comorbidities, anxiety, depression, IBS symptom severity, and IBS quality of life (QOL).ResultsThe mean age was 41 (SD = 15). Age interacted with medical comorbidities to predict anxiety, F(7,354) = 5.82, p = 0.009, R² = 0.10. Results revealed significant main effects for education, β = − 0.16, p < 0.05, age, β = − 0.15, p < 0.05, medical comorbidities, β = 0.25, p < 0.05, and a significant interaction, β = − 0.15, p < 0.01. Anxiety was greater among patients with many comorbidities, with this effect being more pronounced for younger adults. Depression, also predicted by the interaction between age and comorbidities, showed the same pattern as anxiety. There was no significant interaction between age and medical comorbidities in predicting IBS symptom severity or IBS QOL.ConclusionDistress among IBS patients with medical comorbidities varies with age, with higher levels of anxiety and depression among younger adults than their older counterparts. Medical comorbidity may have a more selective impact on psychological distress as compared to IBS symptom severity and quality of life for younger adults with IBS. Distress may increase IBS burden for these patients and complicate its medical management.     

Outcomes of middle fossa craniotomy for the repair of superior semicircular canal dehiscence

Superior semicircular canal dehiscence (SSCD) is a rare defect of the arcuate eminence that causes an abnormal connection between the superior semicircular canal and middle cranial fossa. Patients often present with a variety of auditory and vestibular symptoms. Trigger avoidance is the initial strategy, but surgery may be necessary in debilitating cases. We retrospectively reviewed SSCD patients undergoing repair via a middle fossa craniotomy between March 2011 and September 2015. Forty-nine patients undergoing 58 surgeries were identified. Autophony was the most common symptom at presentation (n = 44; 90%). Mean follow-up was 10.9 months, with 100% of patients reporting resolution of at least one symptom. Aural fullness was the most commonly resolved symptom following surgical repair (n = 19/22; 86%). Hearing loss (n = 11/25; 44%) and tinnitus (n = 11/38; 29%) were the most common symptoms to persist following surgery. The most common symptom to develop after surgery was disequilibrium (n = 4/18; 22%). Upon comparing the overall pre-operative and post-operative groups, the number of patients with autophony (p < 0.0001), aural fullness (p = 0.0006), hearing loss (p = 0.0119), disequilibrium (p = 0.0002), sound- and pressure-induced vertigo (p < 0.0001), and tinnitus (p < 0.0001) were significantly different. Improved clinical outcomes were demonstrated in patients undergoing SSCD repair through a middle cranial fossa approach. The most common presenting symptom (autophony) was also most likely to resolve after surgery. Hearing loss is less amenable to surgical correction. Disequilibrium developed in a small number of patients after repair.     

Afferent control of walking: Are there distinct deficits associated to loss of fibres of different diameter?

ObjectivesTo compare the gait pattern in patients affected by different types of neuropathy.MethodsWe recruited healthy subjects (HS, n = 38), patients with Charcot–Marie–Tooth disease type 1A (CMT1A) (n = 10) and patients with diabetic neuropathy (DNP) (n = 12). Neuropathy impairment score and neuropathy score were assessed. Body sway during quiet stance, and spatio-temporal gait parameters were recorded.ResultsMost patients had reduced or absent tendon-tap reflexes. Strength of foot dorsiflexor muscles (p < 0.05) and conduction velocity (CV) of leg nerves (p < 0.0001) were more impaired in CMT1A than DNP, whereas joint-position sense was more affected (p < 0.05) in DNP. Body sway while standing was larger in DNP compared to CMT1A and HS (p < 0.01 and p < 0.0001 respectively). During gait, the distribution of foot sole contact pressure was abnormal in CMT1A (p < 0.05) but not in DNP. Velocity and step length were decreased, and foot yaw angle at foot flat increased, in DNP with respect to CMT1A and HS (both variables, p < 0.001). Gait velocity and step length were decreased (p < 0.005) also in CMT1A, but to a smaller extent than in DNP, so that the difference between patient groups was significant (p < 0.0005). Duration of the double support was protracted in DNP compared to CMT1A and HS (p < 0.0005). For DNP only, velocity of gait and duration of single support were correlated (p < 0.05) both to sway path and lower limb muscle strength.ConclusionsChanges in both body sway and stance phase of gait were larger in DNP than CMT1A, indicating more impaired static and dynamic control of balance when neuropathy affects the small in addition to the large afferent fibres. Diminished somatosensory input from the smaller fibres rather than muscle weakness or foot deformity plays a critical role in the modulation of the support phase of gait.SignificanceThe analysis of balance and gait in patients with neuropathy can offer a tool for understanding the nature and functional impact of the neuropathy and should be included in their functional evaluation.     

Prevalence of restless legs syndrome among adults in Iceland and Sweden: Lung function, comorbidity, ferritin, biomarkers and quality of life

ObjectiveThis study investigates the prevalence and the association between restless legs syndrome (RLS) and a large variety of health variables in two well-characterized random samples from the general population in Reykjavik, Iceland, and Uppsala, Sweden.MethodsUsing the national registries of inhabitants, a random sample from adults aged 40 and over living in Reykjavík, Iceland (n = 939), and Uppsala, Sweden (n = 998), were invited to participate in a study on the prevalence of COPD (response rate 81.1% and 62.2%). In addition, the participants were asked to answer the following questionnaires: International RLS Rating Scale, Short Form-12, the Epworth Sleepiness Scale, and questions about sleep, gastroeosophageal reflux, diabetes and hypertension, as well as pharmacological treatment. Interleukin-6 (IL-6), C-reactive protein (CRP) and ferritin were measured in serum.ResultsRLS was more commonly reported in Reykjavik (18.3%) than in Uppsala (11.5%). Icelandic women reported RLS almost twice as often as Swedish women (24.4 vs. 13.9% p = 0.001), but there was no difference in prevalence of RLS between Icelandic and Swedish men. RLS was strongly associated with sleep disturbances and excessive daytime sleepiness. Subjects with RLS were more likely to be ex- and current smokers than subjects without RLS (p < 0.001). Respiratory symptoms and airway obstruction were more prevalent among those reporting RLS and they also estimated their physical quality of life lower than those without RLS (p < 0.001). RLS was not associated with symptoms of the metabolic syndrome like hypertension, obesity, markers of systemic inflammation (IL-6 and CRP) or cardiovascular diseases. Ferritin levels were significantly lower in RLS participants (p = 0.0002), but not (p = 0.07) after adjustment for center, age, sex and smoking history.ConclusionRestless legs syndrome was twice as common among Icelandic women compared to Swedish women. No such difference was seen for men. RLS was strongly associated with smoking and respiratory symptoms, decreased lung function, sleep disturbances, excessive daytime sleepiness, and physical aspects of life quality. RLS was not associated with markers of the metabolic syndrome like hypertension, obesity, cardiovascular diseases or biomarkers of systemic inflammation.     

Predictors and patterns of insomnia symptoms in OSA before and after PAP therapy

ObjectiveIdentify factors that predict improvement versus persistence of insomnia symptoms following treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) therapy.MethodsArchival data from 68 PAP-treated sleep apnea patients aged 25–83 were analyzed using nonparametric tests and stepwise regression to assess the relationships between insomnia symptoms, multiple OSA variables, and PAP use over time.ResultsPretreatment insomnia symptom severity (ISS; b = −0.72, p < 0.001), PAP average use (b = −0.01, p = 0.01) and respiratory disturbance index (RDI; b = −0.02, p = 0.03) predict change in insomnia following PAP therapy. Forty-five percent (24/53) of the subjects with moderate to severe insomnia at pretreatment reported no/mild symptoms after PAP therapy and were considered improved. Improved subjects had lower pretreatment ISS (p < 0.001), higher RDI (p = 0.01), and higher average PAP use (p < 0.035) than subjects with persistent insomnia. Number of medications and comorbidities were similar between improved and persistent groups. New onset of insomnia symptoms occurred in 13% (2/15) of the patients with no/mild pretreatment insomnia.ConclusionsAlthough ISS declines following PAP treatment, 55% of OSA patients have persistent moderate to severe symptoms despite treatment. More severe OSA is linked to higher likelihood of insomnia improvement and the effect of PAP therapy on insomnia may be mediated by OSA severity. Persistent insomnia is unrelated to medication use or comorbidities and may represent an independent, self-sustaining disorder requiring targeted intervention.     

Impact of sleeping position on central sleep apnea/Cheyne–Stokes respiration in patients with heart failure

BackgroundThe present study determines the influence of sleeping position on central sleep apnea (CSA) in patients with heart failure (HF).MethodsThe apnea/hypopnea index (AHI) during different body positions while asleep was examined by cardiorespiratory polygraphy in 71 patients with HF (ejection fraction <45%).ResultsTwenty-five of the patients having predominantly CSA (central apnea index ?10/h) with a lower obstructive apnea index (<5/h) were assigned to groups with positional (lateral to supine ratio of AHI <50%, n = 12) or non-positional (ratio ?50%, n = 13) CSA. In the non-positional group the BNP level was higher, the ejection fraction was lower and the trans-tricuspid pressure gradient was higher than in the positional group. Multiple regression analysis revealed more advanced age (p = 0.006), log₁₀ BNP (p = 0.017) and lung-to-finger circulation time (p = 0.020) as independent factors of the degree of positional CSA. Intensive treatment for HF changed CSA from non-positional to positional in all eight patients tested. Single night of positional therapy reduced CSA (p < 0.05) and BNP level (p = 0.07) in seven positional patients.ConclusionAs cardiac dysfunction progresses, severity of CSA also increases and positional CSA becomes position-independent. Positional therapy could decrease CSA, thereby having a valuable effect on HF.     

Elevated C-reactive protein is associated with severe periodic leg movements of sleep in patients with restless legs syndrome

BackgroundRestless legs syndrome (RLS) is a common sleep disorder in which urges to move the legs are felt during rest, are felt at night, and are improved by leg movement. RLS has been implicated in the development of cardiovascular disease. Periodic leg movements (PLMs) may be a mediator of this relationship. We evaluated systemic inflammation and PLMs in RLS patients to further assess cardiovascular risk.Methods137 RLS patients had PLM measurements taken while unmedicated for RLS. Banked plasma was assayed for high sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha).ResultsMean (SD) PLM index was 19.3 (22.0). PLMs were unrelated to TNF-a and IL-6, but were modestly correlated with log CRP (r(129) = 0.19, p = 0.03). Those patients with at least 45 PLMs/h had an odds ratio of 3.56 (95% CI 1.26–10.03, p = 0.02, df = 1) for having elevated CRP compared to those with fewer than 45 PLMs/h. After adjustment for age, race, gender, diabetes, hypertension, hyperlipidemia, inflammatory disorders, CRP-lowering medications, and body mass index, the OR for those with ?45 PLMs/h was 8.60 (95% CI 1.23 to 60.17, p = 0.03, df = 10).ConclusionsPLMs are associated with increased inflammation, such that those RLS patients with at least 45 PLMs/h had more than triple the odds of elevated CRP than those with fewer PLMs. Further investigation into PLMs and inflammation is warranted.     

Verbal fluency as a possible predictor for psychosis

BackgroundNeurocognitive abnormalities are prevalent in both first episode schizophrenia patients and in ultra high risk (UHR) patients.AimTo compare verbal fluency performance at baseline in UHR in patients that did and did not make the transition to psychosis.MethodBaseline verbal fluency performance in UHR-patients (n = 47) was compared to match first episode patients (n = 69) and normal controls (n = 42).ResultsVerbal fluency (semantic category) scores in UHR-patients did not differ significantly from the score in first episode schizophrenia patients. Both the UHR group (p < 0.003) and the patient group (p < 0.0001) performed significantly worse than controls. Compared to the non-transition group, the transition group performed worse on verbal fluency, semantic category (p < 0.006) at baseline.ConclusionsVerbal fluency (semantic category) is disturbed in UHR-patients that make the transition to psychosis and could contribute to an improved prediction of transition to psychosis in UHR-patients.     

Stigmatizing attitudes and social perception towards mental illness among Moroccan medical students

ObjectivesThis study aimed to explore medical students’ attitudes, social perception, and knowledge towards mental illness and identify the associated factors.MethodsA cross-sectional study was conducted in the Medical Faculty of Fez. A representative sample of 420 Moroccan students from the first to the seventh years was selected randomly during the academic year (2018/2019). They completed the Mental Illness Clinicians Attitudes scale (MICA) and a self-questionnaire exploring sociodemographic data, the university course, social perception and knowledge towards mental illness, and the potential consideration of psychiatry as a career.ResultsThe average age of participants was 21.73 years (SD ± 2.60), and 72.4% (n = 304) of respondents were female (M/F gender ratio = 0.39). The participants held stigmatizing attitudes and negative social perceptions towards mental illness, as indicated by the high score of the MICA scale (mean = 57.24; SD ± 9.95). Females (p = 0.02) and married students (p = 0.02) showed significantly more tolerant attitudes. The attitudes of students (p = 0.37) who completed the psychiatry clerkship were slightly more favorable (p = 0.15). There was no significant difference in attitudes according to the level of study (p = 0.06). Students with a lower socioeconomic level tended to be less stigmatizing (p = 0.08). The assessment of knowledge about mental illness among students objectified major gaps. A total of 17.9% (n = 75) considered psychiatry as a career.ConclusionThe attitudes of medical students in this study were stigmatizing, and this should without delay motivate Moroccan research, educational and health authorities to investigate further scientific research in this area to address these attitudes and remedies.     

Crosstalk between interleukin-6 and corticotropin-releasing factor modulate submucosal plexus activity and colonic secretion

BackgroundIrritable bowel syndrome (IBS) is a common disorder of the gut with symptoms such as diarrhoea, constipation, abdominal pain and bloating, that are frequently exacerbated by stress. Circulating levels of the pro-inflammatory cytokine, interleukin-6 (IL-6), which can activate colonic enteric neurons, are elevated in IBS patients. These studies aim to explore the relationship between IL-6 and the stress peptide, corticotropin-releasing factor (CRF) in colonic submucosal neurons.MethodsCalcium imaging, Ussing chamber electrophysiology and immunohistochemistry were conducted on rat distal colons to investigate potential crosstalk between IL-6 and CRF.Key resultsColonic secretions from the maternal separation rat model of IBS stimulated increases in intracellular calcium in naïve submucosal neurons via CRF1 receptors (n = 15, p < 0.05). Moreover, IL-6 (n = 50, p < 0.01) but not IL-1β (n = 46, p > 0.05) or TNFα (n = 46, p > 0.05) potentiated the CRF-evoked calcium response. CRF (1 μM, 1 h, n = 5) stimulation also induced colonic secretion of IL-6 and inhibited the pro-secretory effects of IL-6 on colonic ion transfer (n = 12).Conclusions and inferencesThese studies demonstrate the modulatory effects of CRF on colonic IL-6 secretion, neuronal activation and secretory function. These findings may provide an insight into the molecular mechanisms underlying symptom flares in IBS during periods of high stress.     

Adult separation anxiety disorder in complicated grief: an exploratory study on frequency and correlates

IntroductionComplicated grief (CG) has been the subject of increasing attention in the past decades but its relationship with separation anxiety disorder (SEPAD) is still controversial. The aim of the current study was to explore the prevalence and clinical significance of adult SEPAD in a sample of help-seeking individuals with CG.Methods151 adults with CG, enrolled in a randomized controlled trial comparing the effectiveness of (CG) treatment to that of interpersonal therapy, were assessed by means of the Inventory of Complicated Grief (ICG), the Structured Clinical Interview for DSM-IV, the Hamilton Rating Scale for Depression (HAM-D), the Work and Social Adjustment Scale (WSAS), the Adult Separation Anxiety Questionnaire (ASA-27), the Grief Related Avoidance Questionnaire (GRAQ), the Peritraumatic Dissociative Experiences Questionnaire (PDEQ), and the Impact of Events Scale (IES).Results104 (68.9%) individuals with CG were considered to have SEPAD (ASA-27 score ≥22). Individuals with SEPAD were more likely to have reported a CG related to the loss of another close relative or friend (than a parent, spouse/partner or a child) (p = .02), as well as greater scores on the ICG (p = <.001), PDEQ (p = .004), GRAQ (p < .001), intrusion (p < .001) and avoidance (p = <.001) IES subscales, HAM-D (p < .001) and WSAS (p = .006). ASA-27 total scores correlated with ICG (p < .0001), PDEQ (p < .001) GRAQ (p < .0001) scores and both the IES intrusion (p < .0001) and IES avoidance (p < .0001) subscale scores. People with SEPAD had higher rates of lifetime post-traumatic stress disorder (PTSD) (p = .04) and panic disorder (PD) (p = .01).ConclusionsSEPAD is highly prevalent among patients with CG and is associated with greater symptom severity and impairment and greater comorbidity with PTSD and PD. Further studies will help to confirm and generalize our results and to determine whether adult SEPAD responds to CG treatment and/or moderates CG treatment response.     

Topography of sensory symptoms in patients with drug-naïve restless legs syndrome

ObjectivesWe aimed to describe the sensory topography of restless legs syndrome (RLS) sensory symptoms and to identify the relationship between topography and clinical variables.MethodsEighty adult patients with drug-naïve RLS who had symptoms for more than 1 year were consecutively recruited. During face-to-face interviews using a structured paper and pencil questionnaire with all participants, we obtained clinical information and also marked the topography of RLS sensory symptoms on a specified body template, all of which were subsequently inputted into our in-house software. The RLS sensory topography patterns were classified according to localization, lateralization, and symmetry. We investigated if these sensory topography patterns differed according to various clinical variables.ResultsThe lower extremities only (LE) were the most common location (72.5%), and 76.3% of participants exhibited symmetric sensory topography. Late-onset RLS showed more asymmetric sensory distribution compared with early-onset RLS (P = .024). Patients whose sensory symptoms involved the lower extremities in addition to other body parts (LE-PLUS) showed more severe RLS compared with those involving the LE (P = .037).ConclusionRLS sensory symptoms typically were symmetrically located in the lower extremities. LE-PLUS or an asymmetric distribution more often occurred in patients with more severe RLS symptoms or late-onset RLS.     

Exploratory associations with Tumor Necrosis Factor-α, disinhibition and suicidal endorsement after traumatic brain injury

PurposeTo examine the relationship of Tumor Necrosis Factor (TNF)-α to disinhibition and suicidal endorsement after traumatic brain injury (TBI).ParticipantsAdults with moderate to severe TBI (acute serum levels: n = 48, n = 543 samples; acute CSF levels: n = 37, n = 389 samples; chronic serum levels: n = 48, n = 326 samples).Main measuresTNFα levels (CSF, Serum) from time of injury to 12 months post-injury; Frontal Systems Behavior Scale – Disinhibition Subscale at 6 and 12 months post-injury; Patient Health Questionnaire at 6 and 12 months post-injury.ResultsParticipants with TBI had significantly higher CSF and serum TNFα levels than healthy controls (p < 0.05). Acute and chronic serum TNFα was significantly associated with disinhibition at 6 months post-injury (p = 0.009, p = 0.029 respectively), and 6 month disinhibition was associated with suicidal endorsement at both 6 and 12 months (p = 0.045, p = 0.033 respectively) and disinhibition at 12 months post-injury (p < 0.001).ConclusionThese preliminary data suggest a biological to behavioral pathway of suicidality after TBI, from TNFα to disinhibition to suicidal endorsement. Future investigation is warranted to validate these findings and clarify what biological mechanisms might underlie these relationships.     

Efficacy and safety of pramipexole in Japanese patients with primary restless legs syndrome: A polysomnographic randomized,double-blind,placebo-controlled study

ObjectiveTo evaluate the efficacy of pramipexole on polysomnographic measures, patient ratings and a clinical rating in Japanese patients with primary restless legs syndrome (RLS).MethodsPatients with moderate to severe RLS having periodic limb movements in bed index (PLMI) ? 5 were randomly assigned to receive pramipexole or placebo in a 6-week, double-blind, placebo-controlled study with forced titration from 0.125 to 0.75 mg/day. Both polysomnography (PSG) and the suggested immobilization test (SIT) were performed at baseline and 6 weeks after starting treatment.ResultsThe analysis of covariance of log-transformed PLMI showed that the adjusted means at the end of study were significantly smaller in the pramipexole group than in the placebo group (p = 0.0019). In all patients, variables on SIT did not show any differences between the two groups, whereas a significant improvement was shown in the pramipexole group compared with the placebo group for patients with a SIT-PLM index at baseline ? 15. Pramipexole group showed a significant reduction in the International Restless Legs Syndrome Study Group rating scale (IRLS; p = 0.0005), a significant improvement in both Patient Global Impression (PGI; p < 0.0001) and Clinical Global Impressions (CGI-I; p = 0.0488), and a significantly greater mean reduction in the Pittsburgh Sleep Quality Index (PSQI; p = 0.0016), when compared with those of placebo group at week 6.ConclusionsPramipexole is highly efficacious in the reduction of PLMI and in the improvement of subjective severity of RLS and subjective sleep disturbance caused by the disorder.     

A shared low-frequency oscillatory rhythm abnormality in resting and sensory gating in schizophrenia

ObjectivesWe hypothesized that an oscillatory abnormality that is consistently observed across various testing paradigms may index an elementary neuronal abnormality marking schizophrenia risk.MethodsCompared neural oscillations in resting EEG and sensory gating conditions in schizophrenia patients (n = 128), their first-degree relatives (n = 80), and controls (n = 110) and calculated phenotypic and/or genetic correlation of the abnormal measure across these conditions.ResultsUsing a uniform, single trial analytical approach, we identified two prominent oscillatory characteristics in schizophrenia: (1) augmented neural oscillatory power was pervasive in medicated schizophrenia patients in most frequencies, most prominent in the theta–alpha range (4–11 Hz) across the two paradigms (all p < 0.007); and (2) their first-degree relatives shared significantly augmented oscillatory energy in theta–alpha frequency in resting (p = 0.002) and insufficient suppression of theta–alpha in sensory gating (p = 0.01) compared with normal controls. Heritability estimates for theta–alpha related measures for resting and gating conditions ranged from 0.44 to 0.49 (p < 0.03). The theta–alpha measures were correlated genetically with each other (RhoG = 0.82 ± 0.43; p < 0.05).ConclusionsAugmented theta–alpha rhythm may be an elementary neurophysiological problem associated with genetic liability of schizophrenia.SignificanceThis finding helps to refine key electrophysiologic biomarkers for genetic and clinical studies of schizophrenia.