Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder.

BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11 C-donepezil PET) and nigrostriatal dopaminergic function (18 F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. RESULTS: The 11 C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11 C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. CONCLUSION: Reduced neocortical 11 C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.

Effects of CPAP in patients with obstructive apnoea: is the presence of allergic rhinitis relevant?

PURPOSE: The aim of the study is to compare the effects of continuous positive airway pressure (CPAP) on the nasal cavities of patients with obstructive sleep apnoea (OSA) and with or without allergic rhinitis (AR/nonAR). METHODS: This paper is a prospective, longitudinal study. Thirty-four consecutive CPAP treatment-adherent patients with OSA (17 AR and 17 nonAR) were evaluated before and 2 months after treatment, by means of clinical (otorhinolaryngological symptoms, daytime sleepiness, overall and rhinoconjunctivitis-specific quality of life), anatomical (otorhinolaryngological examination), functional (auditory function, tubal function, nasal airflow, and mucociliary clearance), and biological variables (nasal cytology). No humidifier or anti-allergy medicines were used during treatment. RESULTS: Before treatment, patients with AR presented a higher score, compared to nonAR in rhinitis symptoms (4.82 ± 2.53 vs. 0.93 ± 1.02, p = 0.000), otologic symptoms (2.06 ± 1.95 vs. 0.44 ± 0.72, p = 0.004), cutaneous/ocular symptoms (2.12 ± 2.17 vs. 0.65 ± 1.17, p = 0.052), immunoglobulin E (181.82 ± 126.09 vs. 66.13 ± 97.97, p = 0.004), and nasal neutrophils (14.42 ± 31.94 vs. 0.16 ± 0.39, p = 0.031). After treatment, nonAR and AR groups improved in daytime sleepiness (11.53 ± 4.60 vs. 7.53 ± 2.87, p = 0.000 and 13.76 ± 4.93 vs. 7.53 ± 4.41, p = 0.001) respectively and increased nasal neutrophil (0.16 ± 0.39 vs. 5.78 ± 9.43, p = 0.001 and 14.42 ± 31.94 vs. 79.47 ± 202.08, p = 0.035). The symptoms and quality of life improved in patients with AR. NonAR patients, significantly increase nasal dryness (1.65 ± 1.27 vs. 0.00, p = 0.002) and mucociliary clearance times (38.59 ± 24.90 vs. 26.82 ± 23.18, p = 0.016). CONCLUSIONS: CPAP produces inflammation with increased nasal neutrophil levels in AR and nonAR patients. Nevertheless, patients with AR observed an improvement in nasal symptoms and quality of life, whereas in patients without AR, a relevant worsening of nasal dryness and mucociliary transport was observed.

Sexsomnia: parasomnia associated with sexual behaviour during sleep.

INTRODUCTION: The purpose of our study is to describe 4 cases of sexsomnia, a form of parasomnia characterised by sexual behaviour during sleep. METHODS: Clinical history and video-polysomnography recordings from patients diagnosed with sexsomnia in the Multidisciplinary Sleep Unit at Hospital Clínic in Barcelona. RESULTS: Three men and one woman between 28 and 43 years of age reported sexual behaviours during sleep with progression times ranging from 9 months to 7 years. Episodes consisted of masturbation without seeking the participation of a sleeping partner (2 cases) and attempts at sexual intercourse with inappropriate and uncharacteristic vocalizations and behaviours (3 cases). The frequency of the episodes ranged from 4 isolated episodes to 2-3 per week. Patients were amnestic of these events and surprised by their partners' accounts of their behaviour. Medical histories revealed that 1 patient was a somnambulist, 2 had confusional arousals, and 1 experienced somniloquy. Video-polysomnography did not disclose sexual behaviours during sleep but revealed sleep apnoea in 2 cases and periodic leg movements in sleep in another. The only patient treated with clonazepam reported decreased frequency of both confusional arousals and sexsomnia episodes. CONCLUSIONS: Sexsomnia occurs in young adults and is characterised by masturbation and inappropriate attempts at achieving sexual intercourse followed by total amnesia of the events. It can be associated with other parasomnias such as sleepwalking and confusional arousals. Other sleep disorders, including sleep apnoea and periodic leg movement disorder, may trigger episodes of sexsomnia.

Early molecular diagnosis of acute Chagas disease after transplantation with organs from Trypanosoma cruzi-infected donors.

Organ transplantation (TX) is a novel transmission modality of Chagas disease. The results of molecular diagnosis and characterization of Trypanosoma cruzi acute infection in naïve TX recipients transplanted with organs from infected deceased donors are reported. Peripheral blood and cerebrospinal fluid samples from the TX recipients of organs from infected donors were prospectively and sequentially studied for detection of T. cruzi by means of kinetoplastid DNA polymerase chain reaction (kDNA-PCR). In positive blood samples, a PCR algorithm for identification of T. cruzi Discrete Typing Units (DTUs) and quantitative real-time PCR (qPCR) to quantify parasitic loads were performed. Minicircle signatures of T. cruzi infecting populations were also analyzed using restriction fragment length polymorphism (RFLP)-PCR. Eight seronegative TX recipients from four infected donors were studied. In five, the infection was detected at 68.4 days post-TX (36-98 days). In one case, it was transmitted to two of three TX recipients. The comparison of the minicircle signatures revealed nearly identical RFLP-PCR profiles, confirming a common source of infection. The five cases were infected by DTU TcV. This report reveals the relevance of systematic monitoring of TX recipients using PCR strategies in order to provide an early diagnosis allowing timely anti-trypanosomal treatment.

Decreased striatal dopamine transporter uptake in the non-fluent/agrammatic variant of primary progressive aphasia.

BACKGROUND AND PURPOSE: Patients with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) may develop atypical parkinsonian syndromes. However, there is no current biomarker to assess which patients are at high risk of developing parkinsonism. 123I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT)-SPECT detects striatal dopamine dysfunction in vivo. The objective of the present study was to study whether non-fluent/agrammatic patients without parkinsonism at baseline present decreased striatal 123I-FP-CIT uptake. METHODS: Visual and semi-quantitative assessments of the striatal 123I-FP-CIT uptake ratio were carried out in 15 patients with nfvPPA, eight patients with the logopenic variant of PPA (lvPPA) and 18 controls. To rule out progranulin mutations or underlying Alzheimer's disease (AD), serum progranulin levels and cerebrospinal fluid (CSF) biomarkers of AD (Aß42 , total-tau, phosphorylated-tau181 ) were determined. A second 123I-FP-CIT-SPECT analysis in the biomarker-enriched groups was also carried out. RESULTS: Patients with nfvPPA presented reduced striatal 123I-FP-CIT binding, especially in the left hemisphere (P = 0.002), compared with controls. All lvPPA patients had normal striatal 123I-FP-CIT uptake. 123I-FP-CIT striatal binding in nfvPPA patients with normal progranulin and CSF biomarker levels (nfvPPA/bio-) was also significantly reduced (P < 0.05) compared with lvPPA patients with positive AD biomarkers. Sixty-four per cent (9/14) of nfvPPA patients and 80% of nfvPPA/bio- patients (8/10) showed a diminished individual left striatal 123I-FP-CIT uptake ratio. On follow-up, seven nfvPPA/bio- patients developed parkinsonism (median 1.9 years; range 1.2-2.9), six of them with baseline reduced 123I-FP-CIT uptake. CONCLUSIONS: Reduced striatal tracer uptake in nfvPPA patients prior to clinical parkinsonism can be detected by 123I-FP-CIT-SPECT, especially in those with nfvPPA/bio-, suggesting subclinical nigrostriatal degeneration. Decreased striatal 123I-FP-CIT binding might identify PPA patients at increased risk of developing atypical parkinsonian syndromes, probably related to tau-pathology.

Nickel-iron layered double hydroxides for an improved Ni/Fe hybrid battery-electrolyser.

The transition to renewable electricity sources and green feedstock implies the development of electricity storage and conversion systems to both stabilise the electricity grid and provide electrolytic hydrogen. We have recently introduced the concept of a hybrid Ni/Fe battery-electrolyser (battolyser) for this application1. The hydrogen produced during the Ni/Fe cell charge and continued electrolysis can serve as chemical feedstock and a fuel for long-term storage, while the hybrid battery electrodes provide short term storage. Here, we present Ni-Fe layered double hydroxides (NiFe-LDHs) for enhancing the positive electrode performance. The modified Ni(OH)2 material capacity, high rate performance and stability have been tested over a large range of charge rates (from 0.1C to 20C) over 1000 cycles. The Ni-Fe layered double hydroxides allow the capacity per nickel atom to be multiplied by 1.8 in comparison to the conventional ß-Ni(OH)2 material which suggests that the nickel content can be reduced by 45% for the same capacity. This reduction of the nickel content is extremely important as this presents the most costly resource. In addition, Fe doped Ni(OH)2 shows improved ionic and electronic conductivity, OER catalytic activity outperforming the benchmark (Ir/C) catalyst, and long term cycling stability. The implementation of this Fe doped Ni(OH)2 material in the Ni/Fe hybrid battery-electrolyser will bring both electrolysis and battery function forward at reduced material cost and energy loss.

[Dream content in different sleep disorders: sleep apnoea and hypopnoea syndrome, primary insomnia, idiopathic REM sleep behaviour disorder and narcolepsy type 1]. / Contenido onírico en diferentes trastornos del sueño: síndrome de apnea e hipopnea del sueño, insomnio primario, trastorno de la conducta del sueño REM idiopático y narcolepsia de tipo 1.

AIM: The aim of this study is to determine whether there are any differences in the dream content in different sleep disorders and to describe their characteristics. PATIENTS AND METHODS: We studied four sleep disorders: sleep apnoea and hypopnoea syndrome (SAHS), primary insomnia (PI), idiopathic REM sleep behaviour disorder (IRBD) and narcolepsy type I. Each patient was asked to keep a dream diary for two weeks. The content of the diaries was transcribed and analysed for length, mental content, complexity and threat. The results were compared to establish differences. RESULTS: Eighty-nine patients were studied: 23 with SAHS without continuous positive airway pressure (CPAP) who had the highest number of dreams involving threats (32.5%); 19 with SAHS treated with CPAP who had the highest number of dreams involving objects (64.8%), descriptive elements (38%) and higher complexity (9.5%); 22 with primary insomnia who had the highest number of dreams with threatening events in the social sphere (57.7%); 12 with IRBD who had the highest number of dreams with failures (14%) and lower complexity (71.7%); and 13 with narcolepsy type I who had the highest number of dreams related to activities (84.3%) and threats to life (41.4%) These differences were statistically significant (p <0.05). CONCLUSIONS: Different sleep disorders are associated with different dream contents, which would be translating different underlying neurological processes. These findings should be replicated in studies that analyse more patients and add a control group without sleep disorders.

TITLE: Contenido onírico en diferentes trastornos del sueño: síndrome de apnea e hipopnea del sueño, insomnio primario, trastorno de la conducta del sueño REM idiopático y narcolepsia de tipo 1.Objetivo. Determinar si existen diferencias en el contenido onírico en diferentes trastornos del sueño y describir sus características. Pacientes y métodos. Estudiamos cuatro trastornos del sueño: síndrome de apnea e hipopnea del sueño (SAHS), insomnio primario (IP), trastorno de conducta del sueño REM idiopático (TCSRI) y narcolepsia de tipo 1. Se solicitó a cada paciente que llenara un diario de sus sueños durante dos semanas. El contenido de los diarios fue transcrito y analizado en longitud, contenido mental, complejidad y amenaza. Los resultados se compararon para establecer diferencias. Resultados. Se estudió a 89 pacientes: 23 con SAHS sin presión positiva continua de la vía aérea (CPAP) que tuvieron la mayor cantidad de sueños con participación en amenazas (32,5%); 19 con SAHS tratados con CPAP que tuvieron la mayor cantidad de sueños con objetos (64,8%), elementos descriptivos (38%) y de más alta complejidad (9,5%); 22 con insomnio primario con la mayor cantidad de sueños con eventos amenazantes al ámbito social (57,7%); 12 con TCSRI que tuvieron en sus sueños la más alta cantidad de fracasos (14%) y menor complejidad (71,7%), y 13 con narcolepsia de tipo 1 que tuvieron la mayor cantidad de sueños relacionados con actividades (84,3%) y amenazas hacia la vida (41,4 %). Estas diferencias fueron estadísticamente significativas (p menor de 0,05). Conclusiones. Los distintos trastornos del sueño sí se asocian a contenidos oníricos diferentes que traducirían distintos procesos neurológicos subyacentes. Estos hallazgos deberían replicarse en estudios que analicen más pacientes y añadan un grupo control sin trastornos del sueño.

Less invasive surfactant administration reduces incidence of severe intraventricular haemorrage in preterms with respiratory distress syndrome: a cohort study.

OBJECTIVE: Less invasive surfactant administration (LISA) has proved to safely improve morbidity in extreme preterms with respiratory distress syndrome (RDS). Its effect regarding intraventricular hemorrhage (IVH) remains controversial between most recent systematic reviews. We aimed to evaluate its effect over incidence of severe IVH in this population. STUDY DESIGN: We compared the incidence of IVH in a prospective cohort of consecutively born preterm infants <34 weeks' gestation receiving LISA (n = 108) with a historical cohort receiving surfactant delivery via tracheal tube and managed with mechanical ventilation (n = 100). RESULTS: No significant differences regarding perinatal characteristics were observed between both groups. There was a significant reduction in the incidence of severe IVH in LISA group as compared with the historical group [OR = 0.054 (95% CI 0.01-0.2) p = 0.000. NNT 5]. In addition, a significant trend towards decreased mortality was also observed in the study group [OR = 0.2 (95% CI 0.04-0.9) p = 0.027, NNT 9]. Intervention group infants also showed lower oxygenation requirements during the first 72 h post surfactant administration and a reduced incidence of pneumothorax. They were less frequently intubated [31 infants (28.4%) vs. 100 [100%]; P < 0.001] and required fewer days of mechanical ventilation. However, no significant difference in bronchopulmonary dysplasia incidence was observed between both groups. CONCLUSIONS: LISA approach effectively reduces severe IVH in very low and low birth weight (BW) preterms with RDS. In addition we observe a significant trend towards reduction in both need and duration of MV support, air leak, and overall mortality in the intervention group.

Disruption of posterior brain functional connectivity and its relation to cognitive impairment in idiopathic REM sleep behavior disorder.

BACKGROUND: Resting-state functional MRI has been proposed as a new biomarker of prodromal neurodegenerative disorders, but it has been poorly investigated in the idiopathic form of rapid-eye-movement sleep behavior disorder (IRBD), a clinical harbinger of subsequent synucleinopathy. Particularly, a complex-network approach has not been tested to study brain functional connectivity in IRBD patients. OBJECTIVES: The aim of the current work is to characterize resting-state functional connectivity in IRBD patients using a complex-network approach and to determine its possible relation to cognitive impairment. METHOD: Twenty patients with IRBD and 27 matched healthy controls (HC) underwent resting-state functional MRI with a 3T scanner and a comprehensive neuropsychological battery. The functional connectome was studied using threshold-free network-based statistics. Global and local network parameters were calculated based on graph theory and compared between groups. Head motion, age and sex were introduced as covariates in all analyses. RESULTS: IRBD patients showed reduced cortico-cortical functional connectivity strength in comparison with HC in edges located in posterior regions (p <0.05, FWE corrected). This regional pattern was also shown in an independent analysis comprising posterior areas where a decreased connectivity in 51 edges was found, whereas no significant results were detected when an anterior network was considered (p <0.05, FWE corrected). In the posterior network, the left superior parietal lobule had reduced centrality in IRBD. Functional connectivity strength between left inferior temporal lobe and right superior parietal lobule positively correlated with mental processing speed in IRBD (r = .633; p = .003). No significant correlations were found in the HC group. CONCLUSION: Our findings support the presence of disrupted posterior functional brain connectivity of IRBD patients similar to that found in synucleinopathies. Moreover, connectivity reductions in IRBD were associated with lower performance in mental processing speed domain.

Cortical gray matter progression in idiopathic REM sleep behavior disorder and its relation to cognitive decline.

BACKGROUND: Idiopathic Rapid eye movement sleep behavior disorder (IRBD) is recognized as the prodromal stage of the alpha-Synucleinopathies. Although some studies have addressed the characterization of brain structure in IRBD, little is known about its progression. OBJECTIVE: The present work aims at further characterizing gray matter progression throughout IRBD relative to normal aging and investigating how these changes are associated with cognitive decline. METHODS: Fourteen patients with polysomnography-confirmed IRBD and 18 age-matched healthy controls (HC) underwent neuropsychological, olfactory, motor, and T1-weighted MRI evaluation at baseline and follow-up. We compared the evolution of cortical thickness (CTh), subcortical volumes, smell, motor and cognitive performance in IRBD and HC after a mean of 1.6 years. FreeSurfer was used for CTh and volumetry preprocessing and analyses. The symmetrized percent of change (SPC) of the CTh was correlated with the SPC of motor and neuropsychological performance. RESULTS: IRBD and HC differed significantly in the cortical thinning progression in regions encompassing bilateral superior parietal and precuneus, the right cuneus, the left occipital pole and lateral orbitofrontal gyri (FWE corrected, p < 0.05). The Visual form discrimination test showed worse progression in the IRBD relative to HC, that was associated with gray matter loss in the right superior parietal and the left precuneus. Increasing motor signs in IRBD were related to cortical thinning mainly involving frontal regions, and late-onset IRBD was associated with cortical thinning involving posterior areas (FWE corrected, p < 0.05). Despite finding olfactory identification deficits in IRBD, results did not show decline over the disease course. CONCLUSION: Progression in IRBD patients is characterized by parieto-occipital and orbitofrontal thinning and visuospatial loss. The cognitive decline in IRBD is associated with degeneration in parietal regions.

[Sleep-related movement and behavioural disorders in adults]. / Trastornos del movimiento y de la conducta durante el sueño en el adulto.

Sleep-related movement and behaviour disorders may have an impact on sleep quality and lead to daytime symptoms. These groups of conditions include diseases such as restless legs syndrome, periodic leg movements, and REM and NREM parasomnias. The knowledge of their clinical features and management is of utmost importance for the neurologist and sleep specialist. Frequently, these patients are referred to such specialists and it is relevant to know that certain sleep disorders may be associated with other neurological conditions.

TITLE: Trastornos del movimiento y de la conducta durante el sueño en el adulto.Los trastornos del movimiento y de la conducta durante el sueño pueden tener un impacto en la calidad del sueño del paciente y dar lugar a síntomas diurnos. En estos grupos de enfermedades se incluyen entidades como el síndrome de piernas inquietas, los movimientos periódicos de las piernas y las parasomnias del sueño de movimientos oculares rápidos (REM) y no REM. El conocimiento de sus características clínicas y nociones sobre su manejo es de gran importancia para el neurólogo y especialista en sueño por su frecuencia e impacto en la calidad del sujeto. Con frecuencia, estos pacientes son referidos a dichos especialistas, y es relevante conocer que ciertos trastornos del sueño pueden asociarse a otras enfermedades neurológicas.

[Progressive familial intrahepatic cholestasis presenting as liver failure]. / Fallo hepático neonatal como forma de presentación de colestasis intrahepática familiar progresiva.

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomic-recessive inherited cholestatic disorders that begin in the neonatal period or in the first years of life. There are three types of PFIC defined by different mutations located in the gene responsible for the bile flow through the intrahepatic canalicular transporter system. These disorders usually present in children or young adults and the main clinical manifestations are cholestasis, jaundice and pruritus, and they progress slowly towards liver fibrosis in adult life. PFIC diagnosis is based on clinical suspicion, biochemical findings (that include normal gamma-glutamyl transpeptidase in type 1 and 2, but increased levels in type 3), image techniques that rule-out other disorders, and histological confirmation. Initial treatment consists of symptomatic relief of cholestatic symptoms with choleretic agents (urso-deoxycholic acid). Partial biliary derivation and ileal bypass are intermediate therapeutic options. In case of no response to these treatments, liver transplantation is indicated. We report the case of a neonate with PFIC type 2 presenting as a liver failure.

Sleep and sleep disorders in Franz Kafka's narrative works.

OBJECTIVE: As Franz Kafka, one of the most important writers of the 20th century, suffered from severe chronic insomnia disorder and inadequate sleep hygiene that impaired his quality of life, we speculated that sleep disorders would be found in his narrative works. METHODS: We read Kafka's complete literary works looking for references to sleep and sleep disorders, excluding insomnia. RESULTS: In Kafka's works, sleeping well and for a long time was used as an allegory of having a pleasant life. We found that some of his characters were disturbed by excessive daytime sleepiness and sleep attacks, circadian rhythm sleep-wake disorders, sleep-related hallucinations, sleep symptoms in the context of heart failure and abnormal sleep behaviors (eg, sleep-talking, sleep-crying, sleep-laughing and dream-enacting motor manifestations). Kafka also recalled a dream where bruxism occurred. CONCLUSION: Kafka's narrative works contain characters suffering from a wide variety of sleep disorders which in some cases represent autobiographical elements but not in others indicating that he was an astute observer of people, sleep and its disorders. The inclusion of characters suffering from sleep disorders was used by Kafka as a literary resource to enrich his texts.

Umbilical cord milking reduces the risk of intraventricular hemorrhage in preterm infants born before 32 weeks of gestation.

OBJECTIVE: Intraventricular hemorrhage (IVH) is a common complication in extremely preterm infants. We aimed to demonstrate that umbilical cord milking (UCM) would reduce the incidence of IVH in this at risk population. STUDY DESIGN: We compared the incidence of IVH in a prospective cohort of consecutively born preterm infants <32 weeks' gestation receiving UCM (n = 33) with a historical cohort that underwent immediate cord clamping (ICC) (n = 36). RESULTS: No significant differences regarding perinatal characteristics were present between both groups except for chorioamnionitis and preterm rupture of membranes which were more frequent in the UCM group. There was a significant reduction in the incidence of IVH in the UCM group as compared to the ICC group (UCM vs. ICC = 12 vs. 33%, p = 0.037; OR = 0.276 (95% CI 0.079-0.967; p = 0.033; NNT = 4.7) and a reduction in the number of transfusions (UCM vs. ICC = 56 vs. 30%, p = 0.035; OR = 0.348 (0.129-0.938; p = 0.033; NNT = 3.8). UCM was safe for mothers (similar decrease in maternal hemoglobin) and offspring. CONCLUSION: UCM significantly reduced the incidence of IVH in preterm infants < 32 weeks' gestation without associated complications for mother or offspring.

Comparing the accuracy and neuroanatomical correlates of the UPSIT-40 and the Sniffin' Sticks test in REM sleep behavior disorder.

BACKGROUND: Olfactory impairment increases the risk of developing neurodegenerative diseases in patients with idiopathic REM sleep behavior disorder (IRBD). Knowing the test properties of distinct olfactory measures could contribute to their selection for clinical or research purposes. OBJECTIVE: To compare the accuracy in distinguishing IRBD patients from controls with the University of Pennsylvania Smell Identification Test (UPSIT-40) and Sniffin' Sticks Extended test, and to assess the gray-matter volume correlates of these tests. METHOD: Twenty-one patients with IRBD and 27 healthy controls were assessed using both olfactory tests. Independent logistic regressions were computed with diagnosis as a dependent variable and olfactory measures as predictive variables. Receiver operating characteristic curves were computed for each olfactory subtest. Diagnostic accuracy for IRBD was calculated according to the resulting optimal cut-off score. Structural MRI data, acquired with a 3T scanner, were analyzed with voxel-based morphometry. RESULTS: Patients differed from controls in all olfactory measures. The Sniffin-Identification correctly classified 89.1% of cases; the UPSIT-40, 85.4%; the Sniffin-Discrimination, 82.6%; the Sniffin-Total, 81.8%; and the Sniffin-Threshold, 77.3%. Respective AUROC, optimal cut-off, sensitivity, and specificity for each test were: 0.902, ≤26, 85.7%, and 85.2% for the UPSIT-40; 0.884, ≤29, 89.5%, and 76.0% for the Sniffin-Total; 0.922, ≤11, 90.5%, and 88.0% for the Sniffin-Identification; 0.739, ≤4, 73.7%, and 76.0% for the Sniffin-Threshold; and 0.838, ≤11, 85.7%, and 76.0% for the Sniffin-Discrimination. UPSIT-40 scores correlated with gray-matter volumes in orbitofrontal regions in anosmic patients. CONCLUSIONS: UPSIT-40 and Sniffin' Identification showed similar discrimination accuracy, but only the UPSIT-40 showed structural correlates (p ≤ .05 FDR-corrected).

Basic clinical features do not predict dopamine transporter binding in idiopathic REM behavior disorder.

REM sleep behavior disorder (RBD) is strongly associated with development of Parkinson's Disease and other α-synuclein-related disorders. Dopamine transporter (DAT) binding deficit predicts conversion to α-synuclein-related disorders in individuals with RBD. In turn, identifying which individuals with RBD have the highest likelihood of having abnormal DAT binding would be useful. The objective of this analysis was to examine if there are basic clinical predictors of DAT deficit in RBD. Participants referred for inclusion in the RBD cohort of the Parkinson Progression Markers Initiative were included. Assessments at the screening visit including DAT SPECT imaging, physical examination, cognitive function screen, and questionnaire-based non-motor assessment. The group with DAT binding deficit (n = 49) was compared to those without (n = 26). There were no significant differences in demographic or clinical features between the two groups. When recruiting RBD cohorts enriched for high risk of neurodegenerative disorders, our data support the need for objective biomarker assessments.

Pathological description of a non-motor variant of multiple system atrophy.

Multiple system atrophy (MSA) is a neurodegenerative disorder that usually presents clinically as a combination of parkinsonism, cerebellar syndrome and autonomic failure. Patients with MSA can present other clinical features, such as inspiratory stridor and rapid eye movement (REM) sleep behaviour disorder (RBD). We report a patient with pathologically confirmed MSA who presented with a longstanding history of stridor, RBD and autonomic disturbances but did not develop overt parkinsonism or cerebellar signs. This case illustrates that MSA may present clinically without its cardinal motor symptoms, and that stridor and RBD may be clues to recognise the disease in a patient with autonomic failure.

The insomnia of Franz Kafka.

OBJECTIVE: To characterize the insomnia suffered by Franz Kafka (1883-1924), one of the most important literary figures of the 20th century. METHODS: We read Kafka's diaries and private correspondence to his fiancée, friends, editors and relatives looking for references to his insomnia. RESULTS: We found 292 references to insomnia indicating that Kafka suffered from chronic insomnia disorder that originated from and was maintained by the following predisposing and precipitating factors: (1) a complex personality predisposing to an increased arousal level, (2) intrusive thoughts and ruminations at bedtime, (3) excessive worrying about sleep loss and its daytime consequences, and (4) an extraordinary intolerance to noise. Since he could not sleep at night and felt the necessity to compose his literary works in an absolutely quiet environment, Kafka deliberately changed his sleep-wake schedule so he could write at night and nap in the afternoon. These maladaptive sleep habits perpetuated his insomnia and led to chronic sleep deprivation resulting in fatigue, lack of concentration and sleep-related auditory, tactile and visual hallucinations. Kafka sought help in alternative medicine however this was ineffective in improving his insomnia. CONCLUSIONS: Kafka suffered from chronic insomnia disorder and had inadequate sleep hygiene resulting in chronic sleep deprivation. These sleep problems impaired Kafka's quality of life.

Colonic Oxidative and Mitochondrial Function in Parkinson's Disease and Idiopathic REM Sleep Behavior Disorder.

OBJECTIVE: To determine potential mitochondrial and oxidative alterations in colon biopsies from idiopathic REM sleep behavior disorder (iRBD) and Parkinson's disease (PD) subjects. METHODS: Colonic biopsies from 7 iRBD subjects, 9 subjects with clinically diagnosed PD, and 9 healthy controls were homogenized in 5% w/v mannitol. Citrate synthase (CS) and complex I (CI) were analyzed spectrophotometrically. Oxidative damage was assessed either by lipid peroxidation, through malondialdehyde and hydroxyalkenal content by spectrophotometry, or through antioxidant enzyme levels of superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (Gpx1), and catalase (CAT) by western blot. The presence of mitochondrial DNA (mtDNA) deletions was assessed by long PCR and electrophoresis. RESULTS: Nonsignificant trends to CI decrease in both iRBD (45.69 ± 18.15; 23% decrease) and PD patients (37.57 ± 12.41; 37% decrease) were found compared to controls (59.51 ± 12.52, p: NS). Lipid peroxidation was maintained among groups (iRBD: 27.46 ± 3.04, PD: 37.2 ± 3.92, and controls: 31.71 ± 3.94; p: NS). Antioxidant enzymes SOD2 (iRBD: 2.30 ± 0.92, PD: 1.48 ± 0.39, and controls: 1.09 ± 0.318) and Gpx1 (iRBD 0.29 ± 0.12, PD: 0.56 ± 0.33, and controls: 0.38 ± 0.16) did not show significant differences between groups. CAT was only detected in 2 controls and 1 iRBD subject. One iRBD patient presented a single mtDNA deletion.