Problems in functioning from the patient perspective using the International Classification of Functioning, Disability and Health (ICF) as a reference

We conducted a qualitative, multicenter study using a focus group design to explore the lived experiences of persons with any kind of primary sleep disorder with regard to functioning and contextual factors using six open-ended questions related to the International Classification of Functioning, Disability and Health (ICF) components. We classified the results using the ICF as a frame of reference. We identified the meaningful concepts within the transcribed data and then linked them to ICF categories according to established linking rules. The six focus groups with 27 participants yielded a total of 6986 relevant concepts, which were linked to a total of 168 different second-level ICF categories. From the patient perspective, the ICF components: (1) Body Functions; (2) Activities & Participation; and (3) Environmental Factors were equally represented; while (4) Body Structures appeared poignantly less frequently. Out of the total number of concepts, 1843 concepts (26%) were assigned to the ICF component Personal Factors, which is not yet classified but could indicate important aspects of resource management and strategy development of those who have a sleep disorder. Therefore, treatment of patients with sleep disorders must not be limited to anatomical and (patho-)physiological changes, but should also consider a more comprehensive view that includes patient's demands, strategies and resources in daily life and the contextual circumstances surrounding the individual.

Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing narcolepsy. To further define the genetic basis of narcolepsy risk, we performed a genome-wide association study (GWAS) in 562 European individuals with narcolepsy (cases) and 702 ethnically matched controls, with independent replication in 370 cases and 495 controls, all heterozygous for DRB1*1501-DQB1*0602. We found association with a protective variant near HLA-DQA2 (rs2858884; P < 3 x 10(-8)). Further analysis revealed that rs2858884 is strongly linked to DRB1*03-DQB1*02 (P < 4 x 10(-43)) and DRB1*1301-DQB1*0603 (P < 3 x 10(-7)). Cases almost never carried a trans DRB1*1301-DQB1*0603 haplotype (odds ratio = 0.02; P < 6 x 10(-14)). This unexpected protective HLA haplotype suggests a virtually causal involvement of the HLA region in narcolepsy susceptibility.

Latrepirdine stimulates autophagy and reduces accumulation of α-synuclein in cells and in mouse brain

Latrepirdine (Dimebon; dimebolin) is a neuroactive compound that was associated with enhanced cognition, neuroprotection and neurogenesis in laboratory animals, and has entered phase II clinical trials for both Alzheimer's disease and Huntington's disease (HD). Based on recent indications that latrepirdine protects cells against cytotoxicity associated with expression of aggregatable neurodegeneration-related proteins, including Aβ42 and γ-synuclein, we sought to determine whether latrepirdine offers protection to Saccharomyces cerevisiae. We utilized separate and parallel expression in yeast of several neurodegeneration-related proteins, including α-synuclein (α-syn), the amyotrophic lateral sclerosis-associated genes TDP43 and FUS, and the HD-associated protein huntingtin with a 103 copy-polyglutamine expansion (HTT gene; htt-103Q). Latrepirdine effects on α-syn clearance and toxicity were also measured following treatment of SH-SY5Y cells or chronic treatment of wild-type mice. Latrepirdine only protected yeast against the cytotoxicity associated with α-syn, and this appeared to occur via induction of autophagy. We further report that latrepirdine stimulated the degradation of α-syn in differentiated SH-SY5Y neurons, and in mouse brain following chronic administration, in parallel with elevation of the levels of markers of autophagic activity. Ongoing experiments will determine the utility of latrepirdine to abrogate α-syn accumulation in transgenic mouse models of α-syn neuropathology. We propose that latrepirdine may represent a novel scaffold for discovery of robust pro-autophagic/anti-neurodegeneration compounds, which might yield clinical benefit for synucleinopathies including Parkinson's disease, Lewy body dementia, rapid eye movement (REM) sleep disorder and/or multiple system atrophy, following optimization of its pro-autophagic and pro-neurogenic activities.

Natural course of pontocerebellar hypoplasia type 2A

INTRODUCTION Pontocerebellar hypoplasia Type 2 (PCH2) is a rare autosomal recessive condition, defined on MRI by a small cerebellum and ventral pons. Clinical features are severe developmental delay, microcephaly and dyskinesia.Ninety percent carry a p.A307S mutation in the TSEN54-gene. Our aim was to describe the natural course including neurological and developmental features and other aspects of care in a homogeneous group of PCH2 patients all carrying the p.A307S mutation. PATIENTS AND METHODS Patients were recruited via the German patients' organizations. Inclusion criteria were imaging findings of PCH2 and a p.A307S mutation. Data were collected using medical reports and patient questionnaires discussed in a standardized telephone interview. RESULTS Thirty-three patients were included. When considering survival until age 11 years, 53% of children had died Weight, length and head circumference, mostly in the normal range at birth, became abnormal, especially head circumference (-5.58 SD at age 5 yrs). Neurologic symptoms: Choreathetosis was present in 88% (62% with pyramidal signs), 12% had pure spasticity. Epileptic seizures were manifest in 82%, status epilepticus in 39%. Non-epileptic dystonic attacks occurred in 33%. General symptoms: feeding difficulties were recorded in 100%, sleep disorder in 96%, apneas in 67% and recurrent infections in 52%; gastroesophageal reflux disease was diagnosed in 73%, 67% got percutaneous endoscopic gastrostomy and 36% a Nissen-fundoplication. Neurodevelopmental data: All children made progress, but on a low level: such as fixing and following with the eyes was seen in 76%, attempting to grasp objects (76%), moderate head control (73%), social smile (70%), rolling from prone to supine (58%), and sitting without support (9%). Ten percent lost achieved abilities on follow-up. The presence of prenatal symptoms did not correlate with outcome. CONCLUSION Phenotype of this genetically homogeneous group of PCH2 children was severe with reduced survival, but compatible with some developmental progress. Our data support the hypothesis of an early onset degeneration which thereafter stabilizes.

Associação da depressão e distúrbio do sono em pacientes com e sem disfunção temporomandibular

Objective: To evaluate the inter-relationship between TMD (temporomandibular disorder), depression and sleep disorder. Methods: This is a case-control study with questionnaires in 111 patients, allocated from the Dentistry Department of UFRN, Natal, Brazil, from September 2014 to June 2015, for evaluation of depressive symptoms through the BDI (Beck Depression Inventory); sleep disorder, the PSQI (Pittsburgh Sleep Quality Index) and DTM through the RDC / TMD (diagnostic criteria to search for DTM). All indexes were applied by a single examiner previously trained and calibrated. The collected data were analyzed with chi-square tests of Pearson (χ2) and the unconditional logistic regression. Results: women had a risk of 2.85 times more likely to develop TMD (p = 0.046). The OR (odds ratio) shows that sleep disturbance increases by 2.19 the chances of having TMD (p = 0.062) and depressive symptoms increase the risk by 3.16 times in developing dysfunction (p = 0.053). Conclusion: The data of this research allows us to conclude that patients with TMD, in this population, were more likely to develop changes in sleep and depressive symptoms.

Sintomatologia depressiva e sono

Os comportamentos depressivos são cada vez mais evidentes na sociedade atual e ocorrem normalmente, a partir da adolescência, sendo a sua incidência maior nas mulheres. Esses comportamentos, que se traduzem em sintomatologia depressiva interferem com vários aspetos do ser humano, desde a sua imagem corporal, aos seus estados nutricional e psicológico, até ao seu estado de saúde em geral, e ao seu padrão de sono. Este trabalho procura explorar as relações entre os hábitos e a qualidade do sono e a sintomatologia depressiva. Foram avaliados 100 profissionais de saúde com horários de trabalho irregulares e com idades compreendidas entre os 20 e os 65 anos : 54 do sexo feminino e 46 do sexo masculino. Aplicou-se um questionário onde se recolheram os seguintes dados: IMC, horário de trabalho, alimentação, consumo de substâncias estimulantes, sintomatologia depressiva, sonolência diurna e qualidade do sono. Relativamente ao IMC verificou-se que 44% dos inquiridos apresenta excesso de peso e 2% já se encontra em Obesidade grau I. Relativamente ao horário de trabalho, 74 % dos inquiridos referiu o turno da manhã como sendo o seu preferencial e 59% disse que o trabalho por turnos que não era vantajoso. Na avaliação da interferência do horário de trabalho por turnos nas diversas atividades extra profissionais verificou-se que quanto ao tempo de lazer 72 % dos inquiridos disse que interfere muito, na vida social e familiar 78 % dos inquiridos diz que interfere muito, nas atividades pessoais 60 % dos inquiridos disse que interfere muito e na alimentação 83 % dos inquiridos diz que interfere muito. Ainda na alimentação, verificou-se que 52% dos inquiridos acha que o tempo que tem disponível não é adequado a uma boa refeição pelo que se verificou uma frequência das refeições irregular nomeadamente ao pequeno almoço, que apenas 47% disse sempre tomar. Relativamente ao consumo de substâncias estimulantes a mais consumida é o café, uma vez que mais de metade (53%) dos inquiridos diz tomar sempre, segue-se o consumo de tabaco, o qual 44% dos inquiridos disse consumir sempre. Quanto ao exercício físico 68% dos inquiridos disse não praticar. Na presença de sintomatologia depressiva, verifica-se que a maior parte dos inquiridos (68%; n=68) apresenta uma sintomatologia depressiva mínima, 24% apresenta depressão ligeira e 8% (n=8) apresenta depressão moderada. A determinação da sonolência diurna, verifica-se que 28% (n=28) dos inquiridos apresenta pouca sonolência diurna, 65% apresenta moderada sonolência diurna e 7% apresenta Sonolência diurna excessiva. Quanto á qualidade do sono, verifica-se que 18 % dos inquiridos tem uma boa qualidade de sono, 53 % tem sono de má qualidade e 29% dos inquiridos apresenta distúrbio de sono. Estas evidências levaram a concluir que existe uma forte relação ente o sono e a sintomatologia depressiva, e que o horário de trabalho por turnos interfere na qualidade de vida dos indivíduos, sendo que a única forma de intervir está na prevenção, incentivando os trabalhadores a hábitos de vida saudáveis e a um controlo periódico do seu estado de saúde.

Psychiatric Comorbidities in Restless Legs Syndrome.

Restless legs syndrome (RLS) is a neurological sleep disorder with frequent (39%) coexisting psychiatric comorbidities. Patients with any psychiatric comorbidity had fewer periodic leg movements in sleep. Psychiatric disorders should be taken into account in patients with RLS.

Psychiatric symptoms in idiopathic rapid-eye-movement sleep behaviour disorder

Le trouble comportemental en sommeil paradoxal (TCSP) idiopathique est caractérisé par une activité motrice indésirable et souvent violente au cours du sommeil paradoxal. Le TCSP idiopathique est considéré comme un facteur de risque de certaines maladies neurodégénératives, particulièrement la maladie de Parkinson (MP) et la démence à corps de Lewy (DCL). La dépression et les troubles anxieux sont fréquents dans la MP et la DCL. L’objectif de cette étude est d’évaluer la sévérité des symptômes dépressifs et anxieux dans le TCSP idiopathique. Cinquante-cinq patients avec un TCSP idiopathique sans démence ni maladie neurologique et 63 sujets contrôles ont complété la seconde édition du Beck Depression Inventory (BDI-II) et le Beck Anxiety Inventory (BAI). Nous avons aussi utilisé le BDI for Primary Care (BDI-PC) afin de minimiser la contribution des facteurs confondant dans les symptômes dépressifs. Les patients avec un TCSP idiopathique ont obtenu des scores plus élevés que les sujets contrôles au BDI-II (9.63 ± 6.61 vs. 4.32 ± 4.58; P < 0.001), au BDI-PC (2.20 ± 2.29 vs. 0.98 ± 1.53; P = 0.001) et au BAI (8.37 ± 7.30 vs. 3.92 ± 5.26; P < 0.001). Nous avons également trouvé une proportion plus élevée des sujets ayant des symptômes dépressifs (4/63 ou 6% vs. 12/55 ou 22%; P = 0.03) ou anxieux (9/50 or 18% vs. 21/43 ou 49%; P = 0.003) cliniquement significatifs. La proportion des sujets ayant des symptômes dépressifs cliniquement significatifs ne change pas en utilisant le BDI-PC (11/55 or 20%) Les symptômes dépressifs et anxieux sont fréquents dans le TCSP idiopathique. L’examen de routine des patients avec un TCSP idiopathique devrait inclure un dépistage systématique des symptômes dépressifs et anxieux afin de les prévenir ou les traiter.

Sleep bruxism increases the risk for painful temporomandibular disorder, depression and non-specific physical symptoms

To explore the relationship between sleep bruxism (SB), painful temporomandibular disorders (TMD) and psychologic status in a cross-sectional study. The sample consisted of 272 individuals. The Research Diagnostic Criteria for TMD (RDC/TMD) was used to diagnose TMD; SB was diagnosed by clinical criteria proposed by The American Academy of Sleep Medicine. The sample was divided into four groups: (1) patients without painful TMD and without SB, (2) patients without painful TMD and with SB, (3) patients with painful TMD and without SB and (4) patients with painful TMD and with SB. Data were analysed by Odds Ratio test with a 95% confidence interval. Patients with SB had an increased risk for the occurrence of myofascial pain (OR = 5.93, 95% CI: 3.1911.02) and arthralgia (2.34, 1.583.46). Group 3 had an increased risk for moderate/severe depression and non-specific physical symptoms (10.1, 3.6727.79; 14.7, 5.3939.92, respectively), and this risk increased in the presence of SB (25.0, 9.6564.77; 35.8, 13.9491.90, respectively). SB seems to be a risk factor for painful TMD, and this in turn is a risk factor for the occurrence of higher depression and non-specific physical symptoms levels, but a causeeffect relationship could not be established.

Sleep bruxism and temporomandibular disorder: Clinical and polysomnographic evaluation

Objective: To seek better understanding of chronic musculoskeletal facial pain and its relation to sleep bruxism, by comparing patients with sleep bruxism, with and without temporomandibular disorder. Design: Forty sleep bruxism patients were evaluated according to the Research Diagnostic Criteria for Temporomandibular Disorders: group A-20 patients with myofascial pain, 3 men, 17 women; average age 32.7 yr; mean duration of pain 4.37 yr; group B-20 without myofascial pain, 5 men, 15 women; average age 30.8 yr. Sleep and bruxism were evaluated in one-night polysomnography. Results: There were no statistically significant differences for bruxism and sleep variables of the two groups: number of bursts and bruxism episodes per hour, amplitude and duration of bruxism episodes, sleep efficiency and latency, percentage of non-REM and REM sleep, respiratory events, periodic limb movements, and micro-arousals. Conclusions: The polysomnographic characteristics of patients with sleep bruxism, with and without orofacial pain, are similar. More studies are necessary to clarify the reasons why some sleep bruxism patients develop chronic myofascial pain, and others do not. © 2006 Elsevier Ltd. All rights reserved.

REM sleep behavior disorder in Parkinson's disease: a questionnaire-based survey

REM sleep behavior disorder (RBD) is reported in up to 50% of patients with Parkinson's disease (PD). Only a few systematic, large-scale studies have addressed the characteristics of RBD in PD. The aim of the present study is to assess the frequency of RBD in patients with PD and the association with PD characteristics.

Isolated mediotegmental lesion causing narcolepsy and rapid eye movement sleep behaviour disorder: a case evidencing a common pathway in narcolepsy and rapid eye movement sleep behaviour disorder

Narcolepsy is usually an idiopathic disorder, often with a genetic predisposition. Symptomatic cases have been described repeatedly, often as a consequence of hypothalamic lesions. Conversely, REM (rapid eye movement) sleep behaviour disorder (RBD) is usually a secondary disorder, often due to degenerative brain stem disorders or narcolepsy. The case of a hitherto healthy man is presented, who simultaneously developed narcolepsy and RBD as the result of an acute focal inflammatory lesion in the dorsomedial pontine tegmentum in the presence of normal cerebrospinal fluid hypocretin-1 levels and in the absence of human lymphocyte antigen haplotypes typically associated with narcolepsy and RBD (DQB1*0602, DQB1*05). This first observation of symptomatic narcolepsy with RBD underlines the importance of the mediotegmental pontine area in the pathophysiology of both disorders, even in the absence of a detectable hypocretin deficiency and a genetic predisposition.

Sleepwalking, REM sleep behaviour disorder and overlap parasomnia in patients with Parkinson's disease

BACKGROUND/AIMS In a questionnaire survey, we identified 36 (9%) of 417 Parkinson's disease (PD) patients with sleepwalking (SW); 72% of them also had a history of REM sleep behaviour disorder (RBD). We aimed to assess the clinical and polysomnographic characteristics of SW in PD and to compare them to patients with PD with and without a history of RBD. METHODS We performed video-polysomnography and detailed clinical examination in 30 PD patients from the above-mentioned survey: 10 patients with a history of SW, 10 patients with a history of RBD, and 10 patients with no history of either SW or RBD. RESULTS PD patients with SW had higher depression, anxiety and Hoehn & Yahr scores and lower activities of daily living scores than patients without a history of RBD but did not differ from patients with RBD. Patients with SW and RBD also had more often dyskinesia and hallucinations. By polysomnography, RBD was observed in 8 patients with SW and in all patients with a history of RBD. A total of 5 patients without a history of either SW or RBD had REM sleep without atonia without behavioural peculiarities. CONCLUSION SW in PD is associated with depression, higher disease severity and functional disability. The simultaneous occurrence of SW and RBD (overlap parasomnia) in most patients suggests a common underlying disturbance of motor control during sleep in PD, with variable manifestations in different sleep stages.