Loss Of Muscle Tone Research Articles

Etiopathogenesis and Neurobiology of Narcolepsy: A Review

Narcolepsy is a chronic lifelong sleep disorder and it often leaves a debilitating effect on the quality of life of the sufferer. This disorder is characterized by a tetrad of excessive daytime sleepiness, cataplexy (brief loss of muscle tone following strong emotion), hypnogogic hallucinations and sleep paralysis. There are two distinct subgroups of Narcolepsy: Narcolepsy with cataplexy and Narcolepsy without cataplexy. For over 100 years, clinicians have recognised narcolepsy, but only in the last few decades have scientists been able to shed light on the true cause and pathogenesis of narcolepsy. Recent studies have shown that a loss of the hypothalamic neuropeptide Hypocretin/Orexincauses Narcolepsy with cataplexy and that an autoimmune mechanism may be responsible for this loss. Our understanding of the neurophysiologic aspect of narcolepsy has also significantly improved. The basic neural mechanisms behind sleepiness and cataplexy, the two defining symptoms of narcolepsy have started to become clearer. In this review, we have provided a detailed account of the key aspects of etiopathogenesis and neurobiology of narcolepsy, along with a critical appraisal of the more recent and interesting causal associations.We have also looked at the contributions of neuroimaging to the etiopathogenesis of Narcolepsy.

Optogenetic and pharmacogenetic probing of rapid eye movement (REM) sleep circuitry

Introduction Rapid eye movement (REM) sleep is characterized by the activation of cortical electroencephalogram (EEG) and loss of muscle tone (atonia). The exact neuronal circuit mediating the generation and timing of this state is not fully understood. The subcoeruleus (Sub-C) neurons are hypothesized to generate REM sleep and its characteristics. Here we aimed to determine how optogenetics and pharmacogenetic stimulation impacts REM sleep expression. Materials and methods Study#1: To precisely control the neuronal activity of the Sub-C region, we bilaterally infused 200 nL of an adeno-associated viral vector (AAV) containing a light-sensitive opsin (AAV-hsyn- hChR2(H134R)-eYFP) virus into the Sub-C of 4 mice. Animals were instrumented for EEG and EMG recordings. Neurons were stimulated with short blue light pulses (5 ms) at 1 and 10 Hz either independently of behavioral state or specifically during REM sleep. Study#2: To stimulate the Sub-C population for longer time periods, we bilaterally microinjected 400 nL of an AAV harboring a modified muscarinic G-protein coupled receptor (AAV-HSYN-HA-hm3D(Gq)- IRES-mCitrine) into the Sub-C of 3 mice. Administration of clozapine-N-oxide (CNO, 5 mg/kg) activated neurons in the Sub-C. Only animals that had histological verification of ChR2 and hm3D(Gq) receptor expression in the Sub-C region were used for analysis. Results We found that semi-chronic bilateral light activation of Sub-C neurons at 10 Hz, but not 1 Hz, triggered REM sleep-like EEG activity (theta, 4–8 Hz) during light stimulation, and increased EEG Theta power by 64 ± 16% compared to baseline. Under some conditions, light stimulation prolonged the duration of REM sleep episodes by almost 2-fold. Pharmacogenetic manipulation of the neurons in the Sub-C caused a change in behavioural phenotype where the distribution of EEG frequencies shifted towards a REM sleep-like pattern (theta, 4–8 Hz) independent of the behavioural state. Moreover, the average duration of REM sleep-like periods were greater than REM sleep periods under control condition (i.e., saline). Conclusion These results support the hypothesis that the Sub-C region is involved in controlling REM sleep and its associated phenomena. Acknowledgements This research was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC) , the Canadian Institutes of Health Research (CIHR) and the CIHR Sleep and Biological Rhythms Toronto .

Dosing high-risk calves at processing with Lactipro decreases the number of calves treated for bovine respiratory disease (2013)

Bovine respiratory disease is the leading cause of cattle mortalities in U.S. feedlots. In addition to costs associated with death loss and medical treatments, cattle affected by respiratory disease typically have suboptimal performance. Lightweight calves coming into the feedlot are at high risk for respiratory disease due to the stress associated with weaning, transportation, feed and water deprivation, commingling, castration, and other factors. Calves often have no experience eating from feed bunks and may be unfamiliar with the types of feeds used in feedlots. At the same time, the cattle are susceptible to acidosis due to the concentrate-based diets that are fed, which also can have unfavorable effects on feed intake and performance. Moreover, symptoms of acute acidosis, which include poor appetite, increased respiration rate, lethargy, depression, loss of muscle tone, nasal and ocular discharge, and diarrhea, can be difficult to distinguish from clinical symptoms of respiratory disease. Therapies designed to address respiratory disease are generally ineffective for treating acidosis, inevitably leading to the perception that antibiotic treatments have only limited efficacy. Moreover, acidosis can increase susceptibility of cattle to respiratory disease. Acidosis is most logically dealt with through preventive measures. We hypothesized that Lactipro (MS Biotec; Wamego, KS), a source of the lactate-utilizing bacterium Megasphaera elsdenii, could decrease the incidence of feedlot acidosis in newly arrived feedlot calves. By preventing acidosis, we speculated that clinical symptoms similar to those associated with respiratory disease would be less prevalent, thus decreasing the number of animals inappropriately diagnosed and treated for respiratory disease. Our objective was to determine if dosing cattle with Lactipro at processing would decrease morbidity and mortality in lightweight calves after arrival at the feedlot.

Estudo anatômico de bolsões adiposos na região hipogástrica

BACKGROUND: In lipodystrophies of the anterior abdominal wall, variables such as genetic factors, weight gain, age, and loss of muscle tone, either alone or in combination, determine generalized aesthetic changes or changes localized in the epigastrium, hypogastrium, or both. The aim of this study was to describe the limits, distribution, and dimensions of fat bags in the hypogastrium, as well as their anatomic relationships with the neighboring structures. METHODS: Fifty-seven anatomical specimens were dissected from patients undergoing abdominoplasty, during which the hypogastrium was resected en bloc. Moreover, the anterior abdominal wall was also dissected in 8 cadavers. In all samples, the lamellar layer was resected, keeping the dermis-epidermis, areolar layer, and superficial fascia intact. RESULTS: In all specimens, 2 symmetrical adipose clusters were observed bilaterally in the areolar layer, which were in the shape of a bag and had peculiar coloration. These bags were analyzed in relation to their neighboring tissues: the skin, superficial fascia, and deep fat layer. CONCLUSIONS: The lamellar layer was considered as a structural base of the skin, owing to its thinness. The areolar layer showed accumulations and varying amounts of fat in the various body regions without precise limits, which were particularly observed in dissections of the lower abdominal wall and identified by their elasticity, volume, and coloration.

Cord around the neck syndrome

A nuchal cord (or Cord-Around-the Neck (CAN)) occurs when the umbilical cord becomes wrapped around the fetal neck 360 degrees. Nuchal cords are very common, the incidence of nuchal cord increases with advancing gestation from 12% at 24 to 26 weeks to 37% at term [1]. Most are not associated with perinatal morbidity and mortality. In some fetuses and newborns CAN may cause problems, especially when the cord is tightly wrapped around the neck. The cluster of cardiorespiratory and neurological signs and symptoms associated with unique physical features that occur secondary to tight cord-round-the-neck has been referred to as 'tCAN syndrome' (tight Cord Around the Neck Syndrome) [2]. A small number of studies have shown that nuchal cord and or tCAN can affect the outcome of delivery and may have long-term effects on the infant [3] and but as a causative factor for stillbirth it is debatable [4,5]. However, some case reports of postmortem findings on stillbirths show negative pathology reports and tight cord around the neck being the only cause of death [6]. It is the unique physical features of tCAN syndrome that distinguishes it from birth asphyxia even though there are many similarities between these two conditions. Umbilical cord abnormalities are considered as one of the causative factor for birth asphyxia. The manifestation of tCAN symptomatology seems to happen both in the presence of normal and depressed AGPAR scores [7]. Umbilical cord compression due to tCAN may cause obstruction of blood flow first in thin walled umbilical vein, while infant’s blood continues to be pumped out of baby through the thicker walled umbilical arteries thus causing hypovolemia and hypotension resulting in acidosis [8]. Anemia [9] and mild respiratory distress may occur. Some of these infants may also have facial and conjuctival petechiae [10] and rarely petechiae of the neck and upper part of the chest and skin abrasion of neck [11] where the cord was tightly wrapped and facial suffusion [12], all of which can also be seen in some postmortem findings of stillbirth infants who had tCAN [Archana Bargaje, personal communication]. If born alive, some of these infants may also be somewhat obtunded with a low tone and have transient feeding difficulties. These findings raise the possibility of transient encephalopathy, which may lead to long-term complications. A stillbirth attributed to a cord problem should have evidence of cord obstruction or circulatory compromise. Other potential causes of stillbirth need to be excluded prior to labelling cord abnormalities as the causative factor, since cord abnormalities seen in more than a third of all normal live births. The tCAN Syndrome may conceptually be similar to strangulation which may result in non lethal problems or death. The pathophysiological mechanisms of strangulation injuries (lethal and non lethal) involves venous, arterial obstruction (arterial spasm due to carotid pressure) in the neck and vagal collapse (increased parasympathetic tone) [13]. This can lead to cerebral stagnation, hypoxia, and unconsciousness, which, in turn, produces loss of muscle tone. The same pathophysiology of strangulation may possibly be applicable to tCAN syndrome in neonates. A study on potentially asphyxiating conditions and spastic cerebral palsy in infants of normal birth weight showed evidence of association of tCAN in children with quadriplegia [14]. Intermittent umbilical cord occlusion in preterm and near term sheep caused a decline in pO2 and pH, and higher PCO2 and altered brain protein synthesis/degradation [6]. Whether human fetal intermittent strangulation by tCAN have similar brain protein alterations and thus long-term effects remains to be seen. Using specific placental histologic criteria for umbilical blood flow restriction in unexplained stillbirth Parast et al [4] showed significant correlation of placental changes of “minimal histologic criteria” with cord accidents (as tCAN is part of cord accidents). Nuchal cords showed highest rates of thrombosis-related placental histopathology and fetal thrombotic vasculopathy and thrombosis seems to be highly specific for cord related stillbirths [4,5].

Obserwacje kliniczne dzieci z napadami bezdechów

AimAssessment of procedurę for children under 3 years of age, referred to Emergency Department due to apnea episodes. MaterialsThe study included 23 patients with a mean age of 6 months, who presented episode of apnea with cyanosis and loss of muscle tone. 21 children were hospitalized afterwards. ResultsEight had a history of choking or vomiting during feeding. Frequent spitting up suggesting gastroesophageal reflux was observed in 5 patients, breath holding spells in 6 and 1 child was vaccinated. During hospitalization in all children laboratory test, abdominal and cranial ultrasonography, ECG and neurological examination were performed. ChestX-ray was performed in 10 patients, echocardiography in 6, 24-hours Holter ECG monitoringin 3, esophageal pH-metry in 1 and 5 patients underwent laryngological examination. Abnormal findings in blood laboratory tests included anaemia in 3 patients, hyperbilirubinemia in 2. In 9 children abnormalities of muscle tonus and delay maturation of motor automatisms were diagnosed, in 3 psychomotor development delay and 2 had abnormal EEG. 8 patients were diagnosed with respiratory or gastrointestinal tract infection. In 4 children apnea episodes recurred during the obsen/ation. All children had monitoring of vital signs. The treatment included administration of methylxanthines and CPAP in 1 patient, an antibiotics in 3, intravenous fluids infusions in 2, erythropoietin therapy in 2 and blood transfusion in 1. ConclusionThe apnea episodes in children could have multifactorial aetiology and the majority of cases require admission to hospital and broaden targeted diagnostic work-up.

Androgen deprivation therapy-associated vasomotor symptoms

Androgen deprivation therapy (ADT) is widely used as standard therapy in the treatment of locally advanced and metastatic prostate cancer. While efficacious, ADT is associated with multiple side effects, including decreased libido, erectile dysfunction, diabetes, loss of muscle tone and altered body composition, osteoporosis, lipid changes, memory loss, gynecomastia and hot flashes. The breadth of literature for the treatment of hot flashes is much smaller in men than that in women. While hormonal therapy of hot flashes has been shown to be effective, multiple non-hormonal medications and treatment methods have also been developed. This article reviews current options for the treatment of hot flashes in patients taking ADT.

Agonal Sequences in 14 Filmed Hangings With Comments on the Role of the Type of Suspension, Ischemic Habituation, and Ethanol Intoxication on the Timing of Agonal Responses

The Working Group on Human Asphyxia has analyzed 14 filmed hangings: 9 autoerotic accidents, 4 suicides, and 1 homicide. The following sequence of agonal responses was observed: rapid loss of consciousness in 10 ± 3 seconds, mild generalized convulsions in 14 ± 3 seconds, decerebrate rigidity in 19 ± 5 seconds, beginning of deep rhythmic abdominal respiratory movements in 19 ± 5 seconds, decorticate rigidity in 38 ± 15 seconds, loss of muscle tone in 1 minute 17 seconds ± 25 seconds, end of deep abdominal respiratory movements in 1 minute 51 seconds ± 30 seconds, and last muscle movement in 4 minutes 12 seconds ± 2 minutes 29 seconds. The type of suspension and ethanol intoxication does not seem to influence the timing of the agonal responses, whereas ischemic habituation in autoerotic practitioner might decelerate the late responses to hanging.

Fatal spontaneous subdural bleeding due to neonatal giant cell hepatitis: a rare differential diagnosis of shaken baby syndrome

A 7-week-old girl showed vomiting after feeding, facial pallor, loss of muscle tone and respiratory depression. An emergency doctor performed successful resuscitation and after arrival in hospital, cranial ultrasound showed left-sided subdural hemorrhage, cerebral edema with a shift of the midline, and a decrease in cerebral perfusion. Ophthalmologic examination showed retinal hemorrhage. In view of this, the doctors suspected shaken baby syndrome and approached the parents with their suspicions, but they denied any shaking or trauma. Despite surgery for the subdural hemorrhage the girl died a few hours later with a severe coagulopathy. Autopsy verified subdural hemorrhage, cerebral edema and retinal hemorrhage, but also revealed intact bridging veins and a lack of optic nerve sheath hemorrhage, therefore shaken baby syndrome could not be proven by autopsy. Histological examination showed severe neonatal giant cell hepatitis as the cause of the severe coagulopathy and the associated spontaneous subdural bleeding. Neonatal giant cell hepatitis may be responsible for unexpected deaths in infancy and, although rarely associated with subdural bleeding, must be considered as a potential differential diagnosis of shaken baby syndrome.

Quality of life for donors after living donor liver transplantation: A review of the literature

Living donor liver transplantation (LDLT) decreases the shortage of liver grafts for patients in need of a liver transplant, but it involves 2 patients: a recipient and a living donor. Despite the magnitude of the procedure for LDLT donors, only a few studies have investigated the effect of LDLT on the quality of life (QOL) of donors. We performed a systematic search of the MEDLINE database to identify peer-reviewed articles assessing QOL in adults after LDLT donation. Nineteen studies describing 768 unique donors met our inclusion criteria for this review. The median number of donors enrolled in each study was 30 (range = 10-143), and the median follow-up period was 10.4 months (range = 3-51.3 months). Before donation, donor QOL was significantly better than that in control adult populations across all measured QOL domains. Within the first 3 months after donation, the physical domains of QOL were significantly worse than the predonation levels, but they returned to baseline levels within 6 months for the majority of patients (80%-93%). Mental domains of QOL remained unchanged throughout the donation process. Common donor concerns after LDLT included bloating, loss of muscle tone, poor body image, and fatigue. In conclusion, according to our review of the existing literature, most LDLT donors return to their baseline QOL within 6 months. However, there is a lack of long-term data on donor QOL after LDLT, and few standardized assessments include measures of common patient concerns. Additional studies are necessary to develop a comprehensive risk profile for LDLT that includes a rigorous assessment of donor QOL.

Narcolepsy presenting as refractory epilepsy

A 12-year-old boy presented with episodes of sudden fall, several times a day for last 6 months. These episodes of 5-10 seconds were associated with upward rolling of eyes. CT scan cranium and EEG were normal. A local practitioner made diagnosis of epilepsy and the child was put on phenytoin and sodium valproate. Even after 4 months of treatment, there was no reduction in symptoms and patient was referred to us. Detailed history revealed that child had a history of excessive daytime sleepiness for past one year. There was no history of sleep paralysis or hallucinations. Preceding emotions did not trigger these episodes of collapse. These events were not associated with change in posture, prolonged standing. There was no history of drug intake, palpitation, headache or anxiety. Anti-epileptic drugs were withdrawn and clinical diagnosis of narcolepsy with cataplexy was made. Overnight polysomnography was done and it was followed by multiple sleep latency test (MSLT) on next morning. Polysomnography was normal, but MSLT revealed sleep latency time of 0.7 minute and 2 episodes rapid eye movement (REM) sleep out of 4 recorded naps of 20 minute each. These findings of MSLT were consistent with narcolepsy. His parents were educated about the importance of scheduled naps, regular sleepwake schedule and overall good sleep hygiene. Modafinil acetamide 100 mg two times a day was given for excessive daytime sleepiness. Clomipramine, 25 mg at bedtime, was given for cataplexy. Clomipramine was withdrawn on subsequent visits. Presently the child is on modafinil alone for past 6 months and all symptoms have subsided. Narcolepsy is often recognised by excessive daytime sleepiness and associated pathological manifestation of REM sleep like cataplexy, sleep paralysis and hypnagogic hallucinations. Automatic behaviours and disrupted nighttime sleep also occur commonly. Out of all REM sleep manifestations, cataplexy is unique to narcolepsy. It is an abrupt and reversible decrease or loss of muscle tone, most frequently elicited by emotion such as laughter, anger or surprise. Any preceding or anticipation of strong

A reply

We would like to thank Drs Belagodu and Kessell for their comments. We agree that our patient selection criteria probably over-identified difficult intubations. Previous difficult intubation has a better positive predictive value (69–78%) than other independent predictive factors. It means that two to three of the nine patients included in the study could not have been really difficult to intubate. We routinely use the Arné Score that has been accepted by our local Society (Societat Catalana d’Anestesiologia, Reanimació i Terapeùtica del dolor, SCARTD) [1]. This test explores difficult intubation (defined as the need for special techniques additional to Macintosh laryngoscopy to intubate the trachea), instead of difficult laryngoscopy alone. It has a better likelihood ratio than Wilson or El Ganzouri tests. Patients with an Arné score ≥ 11, compared to El Ganzouri score ≥ 4 or Wilson score ≥ 4, have the highest probability of being difficult to intubate when the test is positive. The El Ganzouri simplified test has a specifity of 93.8% and sensitivity 64.5% for predicting difficult laryngoscopy in general surgery patients, that is a likelihood ratio of 11 and a probability of a difficult laryngoscopy when the test is positive of around 21%. The Arné test has a 94% specificity and 96% sensitivity for predicting difficult intubation, that is a likelihood ratio of 16 and a probability of a difficult intubation when the test is positive around 25%. The combination of remifentanil, midazolam and topical anaesthesia caused loss of muscle tone and mild airway obstruction in some patients while unstimulated, which may explain the low oxygen saturation before starting the procedure. Respiratory rate was kept above 8 breaths.min−1 by maintaining verbal contact and adjusting the remifentanil infusion. The patients were interviewed the following day after by the authors, which may be an important bias. However, awake intubation requires a climate of confidence and good communication with the patient. We constantly encourage patients to report any discomfort or unpleasant feelings. As patients are concerned about future intubation, we think they would not hesitate to report unpleasant recall. When deciding whether or not to perform awake intubation in patients with low positive scores of difficult intubation prediction, we also take into account further relevant information for patient safety, such as the predicted difficult mask ventilation score [2]. For that reason, we considered the term ‘difficult airway’ more appropriate than ‘difficult intubation’ for the study title.

Epileptic Negative Myoclonus As the Presenting Seizure Type in Rolandic Epilepsy

Epileptic negative myoclonus is an uncommon seizure type characterized by a sudden, brief loss of muscle tone that may lead to falling. It has been associated largely with benign childhood epilepsy with centrotemporal spikes (rolandic epilepsy), although it may also be a feature of other epileptic syndromes. In patients with rolandic epilepsy, epileptic negative myoclonus usually appears during the course of the disease, well after a diagnosis of the epilepsy has been established. Described here are five patients with rolandic epilepsy in which the presenting seizure was falls due to epileptic negative myoclonus. Because developmental delay or neurocognitive problems were present in three of the children, it is possible that epileptic negative myoclonus may be misinterpreted as clumsiness-related falls in some children who actually have undiagnosed rolandic epilepsy.

Very long‐chain acyl‐CoA dehydrogenase deficiency: The effects of accidental fat loading in a patient detected through newborn screening

Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is an autosomal recessive disorder of fatty acid oxidation. The majority of patients with VLCADD can be detected through newborn screening (NBS) with elevated levels of the tetradecanoyl carnitine species. An 11-month-old infant, diagnosed with late-onset VLCADD (genotype: T848C/G1322A) through newborn screening at birth, was admitted with emesis, severe lethargy, limpness in extremities, loss of muscle tone and an elevated CK level. He was mistakenly given Ketocal formula (about 8 g/kg per day long-chain fat-over six times his usual intake) instead of his usual Monogen formula for 2.5 days before being admitted. Once admitted, he was started on Monogen and IV (10% dextrose) fluids. He was discharged home after four days in the hospital without any sequelae of this accidental fat loading event. The report highlights several important points about this particular case and more generally about patients with VLCADD detected through NBS: (1) the amount of time in which patients might become severely symptomatic and the nature of these symptoms after fat loading; (2) the time frame for complete recovery after beginning of treatment; (3) the importance of alerting home-care companies and families about formula delivery errors and their repercussions.

Bispectral Index Monitoring of a Narcolepsy-Cataplexy Episode During Regional Anesthesia

Narcolepsy or Gélineau syndrome is an extremely incapacitating chronic sleep disorder of unknown etiology that is characterized by uncontrollable attacks of deep sleep and is typically associated with cataplexy sudden loss of muscle tone. The Bispectral Index (BIS), an electroencephalographic-derived cerebral monitor, used for monitoring the effects of anesthetic/hypnotic drugs was shown to correlate to various conditions that could influence the eletroencephalogram. We assessed the utility of using BIS for monitoring a possible narcolepsy-cataplexy episode and whether a distinctive BIS profile might offer an early warning of an impending narcoleptic/cataplectic spell. We recorded both hemispheres, using two synchronized BIS-XP monitors, during a narcolepsy-cataplexy episode in a 57-yr-old male patient undergoing lower limb surgery under femoral nerve block regional anesthesia. The patient went through three stages: first a prodromal "intermittent low-vigilance" phase interrupted by high electromyographic activity. This was followed by a second "continuous low-vigilance" phase of BIS around 75 with low electromyographic activity, ending with a third "nonresponsive vigilance" phase of a full-blown narcolepsy-cataplexy episode of BIS around 45 with complete loss of muscle power. The purpose of presenting this report is to emphasize the fact that narcoleptic patients can still run the risk of loss of consciousness with atonia under regional anesthesia, and such an undesirable complication cannot be under-estimated. BIS monitoring is a simple method that could offer an early warning of an imminent episode, with its associated hazards, in patients with narcolepsy-cataplexy undergoing surgery under regional anesthesia.

Craniofacial Profile Assessment in Patients with Obstructive Sleep Apnea

Craniofacial Profile Assessment in Patients with Obstructive Sleep Apnea

Agonal Sequences in Four Filmed Hangings: Analysis of Respiratory and Movement Responses to Asphyxia by Hanging*

The human pathophysiology of asphyxia by hanging is still poorly understood, despite great advances in forensic science. In that context, filmed hangings may hold the key to answer questions regarding the sequence of events leading to death in human asphyxia. Four filmed hangings were analyzed. Rapid loss of consciousness was observed between 13 sec and 18 sec after onset of hanging, closely followed by convulsions (at 14-19 sec). A complex pattern of decerebration rigidity (19-21 sec in most cases), followed by a quick phase of decortication rigidity (1 min 00 sec-1 min 08 sec in most cases), an extended phase of decortication rigidity (1 min 04 sec-1 min 32 sec) and loss of muscle tone (1 min 38 sec-2 min 47 sec) was revealed. Very deep respiratory attempts started between 20 and 22 sec, the last respiratory attempt being detected between 2 min 00 sec and 2 min 04 sec. Despite differences in the types of hanging, this unique study reveals similarities that are further discussed.

Klinische Aspekte der Narkolepsie

The main clinical features of narcolepsy are excessive daytime sleepiness (EDS) and cataplexy. Facultative symptoms are REM sleep-associated sleep paralysis, automatic movements and hypnagogic hallucinations. However, cataplexy characterised by the sudden loss of muscle tone is classified as a REM-sleep symptom. The clinical diagnosis is based on polysomnographic recording of night-time sleep, multiple sleep latency test and maintenance of wakefulness test. Laboratory findings includes specific HLA alleles and decreased level of hypocretin in the cerebrospinal fluid. Therapeutic options are individualised based on the leading symptoms. Stimulants are used to reduce excessive daytime sleepiness while antidepressants are mainly used to treat cataplexy. Gamma-hydroxybutyric acid improves cataplexy but influences also other symptoms. New therapeutic options will be based on the growing knowledge about the biological function of hypocretin.

Structural effectiveness of pharyngeal sleep apnea surgery

Obstructive sleep apnea results from the combination of a structurally small upper airway combined with the loss of muscle tone during sleep. Most therapies aim to reduce apnea severity by increasing airway size and stability. Conceptually, upper airway surgery should be a highly effective method to treat obstructive sleep apnea and other forms of sleep disordered breathing. Although major reconstructive surgeries such as maxillomandibular advancement demonstrate high success rates, more limited forms of surgery often demonstrate significantly lower success rates. Reviews of such surgical procedures have uniformly ignored contributions of the structural effectiveness of surgery. The purpose of the review is to evaluate current knowledge of how surgery for OSA alters structure. The majority of data available on surgical outcomes involve uvulopalatopharyngoplasty. Data demonstrate that pre-morbid surgical anatomy and techniques have significant effects on ultimate outcomes. Further research on structural outcomes for palatopharyngoplasty, as well as other surgical procedures, is needed to improve clinical outcomes.

Jouberin localizes to collecting ducts and interacts with nephrocystin-1

Joubert syndrome and related disorders are autosomal recessive multisystem diseases characterized by cerebellar vermis aplasia/hypoplasia, retinal degeneration and cystic kidney disease. There are five known genes; mutations of which give rise to a spectrum of renal cystic diseases the most common of which is nephronophthisis, a disorder characterized by early loss of urinary concentrating ability, renal fibrosis, corticomedullary cyst formation and renal failure. Many of the proteins encoded by these genes interact with one another and are located at adherens junctions or the primary cilia and or basal bodies. Here we characterize Jouberin, a multi-domain protein encoded by the AHI1 gene. Immunohistochemistry with a novel antibody showed that endogenous Jouberin is expressed in brain, kidney and HEK293 cells. In the kidney, Jouberin co-localized with aquaporin-2 in the collecting ducts. We show that Jouberin interacts with nephrocystin-1 as determined by yeast-2-hybrid system and this was confirmed by exogenous and endogenous co-immunoprecipitation in HEK293 cells. Jouberin is expressed at cell-cell junctions, primary cilia and basal body of mIMCD3 cells while a Jouberin-GFP construct localized to centrosomes in subconfluent and dividing MDCK cells. Our results suggest that Jouberin is a protein whose expression pattern supports both the adherens junction and the ciliary hypotheses for abnormalities leading to nephronophthisis.